Trial Outcomes & Findings for Virtual Reality Therapy for Chronic Low Back Pain (NCT NCT04409353)

NCT ID: NCT04409353

Last Updated: 2025-10-31

Results Overview

The primary outcome for this study will be self-reported pain interference using Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) version 8a. The pain interference scale measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5) with a raw score calculated by a sum of the 8 items ranging from 8 to 40. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Day 30 - baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain interference).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 413 participants
• Primary outcome timeframe: From baseline to day 30
• Results posted on: 2025-10-31

Participant Flow

Participants were recruited from Cedars-Sinai physician partners at outpatient pain clinic, spine center, rheumatology, community partners such as the ACPA and Saban Clinic, and/or pulled directly from the medical record database between September 2020 and October 2023. All enrollment activities were conducted remotely, by telephone and electronic survey. Recruitment spanned from 10/21/2020 to 10/17/2023. 385 total participants were recruited, producing a final analyzable sample N=360.

Of 1,213 screened participants, 413 met inclusion criteria and signed an eConsent form. Of these, only 385 successfully completed the minimum required 4 of 7 screening week surveys and were randomized to treatment.

Participant milestones

Measure	Distraction-Based VR EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Overall Study STARTED	127	127	131
Overall Study Follow-Up Complete	107	111	111
Overall Study COMPLETED	103	100	105
Overall Study NOT COMPLETED	24	27	26

Reasons for withdrawal

Measure	Distraction-Based VR EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Overall Study Discontinued intervention prior to end of follow-up	4	11	6
Overall Study Lost to Follow-up	6	8	7
Overall Study Major surgery during participation window	4	3	3
Overall Study Life event occurred during participation window	3	2	4
Overall Study Lack of Efficacy	4	1	3
Overall Study Adverse Event	2	1	1
Overall Study Disease burden - unable to participate	0	1	1
Overall Study Intervention too complicated	1	0	1

Baseline Characteristics

Virtual Reality Therapy for Chronic Low Back Pain

Baseline characteristics by cohort

Measure	Distraction-Based VR n=127 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=127 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=131 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Total n=385 Participants Total of all reporting groups
Education High School diploma or equivalent (GED)	8 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Education Some College/Certificate	30 Participants n=5 Participants	28 Participants n=7 Participants	35 Participants n=5 Participants	93 Participants n=4 Participants
Age, Continuous	54.9 years STANDARD_DEVIATION 14.6 • n=5 Participants	52.4 years STANDARD_DEVIATION 16.5 • n=7 Participants	54.8 years STANDARD_DEVIATION 15.7 • n=5 Participants	54.1 years STANDARD_DEVIATION 15.6 • n=4 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	81 Participants n=7 Participants	86 Participants n=5 Participants	241 Participants n=4 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	46 Participants n=7 Participants	45 Participants n=5 Participants	144 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	30 Participants n=7 Participants	31 Participants n=5 Participants	93 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	93 Participants n=5 Participants	93 Participants n=7 Participants	95 Participants n=5 Participants	281 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	25 Participants n=5 Participants	29 Participants n=7 Participants	21 Participants n=5 Participants	75 Participants n=4 Participants
Race (NIH/OMB) White	85 Participants n=5 Participants	77 Participants n=7 Participants	89 Participants n=5 Participants	251 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	25 Participants n=4 Participants
Education Upper Secondary (High School)	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Education Vocational/Trade School	10 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	28 Participants n=4 Participants
Education Bachelor's Degree	37 Participants n=5 Participants	36 Participants n=7 Participants	31 Participants n=5 Participants	104 Participants n=4 Participants
Education Some Graduate School or Professional School	8 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	28 Participants n=4 Participants
Education Graduate or Professional School diploma	32 Participants n=5 Participants	37 Participants n=7 Participants	35 Participants n=5 Participants	104 Participants n=4 Participants
Employment Full-time employment	41 Participants n=5 Participants	53 Participants n=7 Participants	38 Participants n=5 Participants	132 Participants n=4 Participants
Employment Not employed	25 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants	81 Participants n=4 Participants
Employment Part-time employment	18 Participants n=5 Participants	17 Participants n=7 Participants	16 Participants n=5 Participants	51 Participants n=4 Participants
Employment Retired	43 Participants n=5 Participants	37 Participants n=7 Participants	41 Participants n=5 Participants	121 Participants n=4 Participants
Marital Status Divorced	19 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants
Marital Status Married	46 Participants n=5 Participants	59 Participants n=7 Participants	57 Participants n=5 Participants	162 Participants n=4 Participants
Marital Status Never married	40 Participants n=5 Participants	34 Participants n=7 Participants	43 Participants n=5 Participants	117 Participants n=4 Participants
Marital Status Separated	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Marital Status Widowed	11 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	23 Participants n=4 Participants
Marital Status Domestic Partner	9 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Income Less than $10,000	6 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	22 Participants n=4 Participants
Income $10,000-$24,999	17 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants	47 Participants n=4 Participants
Income $25,000-$34,999	13 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	21 Participants n=4 Participants
Income $35,000-$49,999	11 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants	34 Participants n=4 Participants
Income $50,000-$74,999	16 Participants n=5 Participants	18 Participants n=7 Participants	15 Participants n=5 Participants	49 Participants n=4 Participants
Income $75,000-$99,999	16 Participants n=5 Participants	16 Participants n=7 Participants	14 Participants n=5 Participants	46 Participants n=4 Participants
Income $100,000-$149,999	14 Participants n=5 Participants	21 Participants n=7 Participants	18 Participants n=5 Participants	53 Participants n=4 Participants
Income $150,000-$199,999	9 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	25 Participants n=4 Participants
Income $200,000 or more	12 Participants n=5 Participants	16 Participants n=7 Participants	10 Participants n=5 Participants	38 Participants n=4 Participants
Income Prefer not to answer	13 Participants n=5 Participants	17 Participants n=7 Participants	20 Participants n=5 Participants	50 Participants n=4 Participants
Average of daily back pain assessments	6.0 units on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	6.0 units on a scale STANDARD_DEVIATION 1.9 • n=7 Participants	6.3 units on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	6.1 units on a scale STANDARD_DEVIATION 1.9 • n=4 Participants
Average low-back pain in past 7 days	5.8 units on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	5.8 units on a scale STANDARD_DEVIATION 1.8 • n=7 Participants	5.9 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants	5.8 units on a scale STANDARD_DEVIATION 1.9 • n=4 Participants
Opioid Use Yes	41 Participants n=5 Participants	36 Participants n=7 Participants	40 Participants n=5 Participants	117 Participants n=4 Participants
Opioid Use No	84 Participants n=5 Participants	90 Participants n=7 Participants	89 Participants n=5 Participants	263 Participants n=4 Participants
Opioid Use Not sure	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Back Pain Severity Yes	92 Participants n=5 Participants	94 Participants n=7 Participants	96 Participants n=5 Participants	282 Participants n=4 Participants
Back Pain Severity No	20 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	61 Participants n=4 Participants
Back Pain Severity Not sure	15 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	42 Participants n=4 Participants
Back Pain Operation Yes, one	20 Participants n=5 Participants	29 Participants n=7 Participants	20 Participants n=5 Participants	69 Participants n=4 Participants
Back Pain Operation Yes, more than one	15 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants	52 Participants n=4 Participants
Back Pain Operation No	92 Participants n=5 Participants	84 Participants n=7 Participants	88 Participants n=5 Participants	264 Participants n=4 Participants
Chronic Pain	3.0 units on a scale STANDARD_DEVIATION 2.0 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 1.9 • n=7 Participants	2.9 units on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 1.9 • n=4 Participants
ITQ score	99.9 units on a scale STANDARD_DEVIATION 18.1 • n=5 Participants	102.2 units on a scale STANDARD_DEVIATION 17.7 • n=7 Participants	99.6 units on a scale STANDARD_DEVIATION 17.7 • n=5 Participants	100.6 units on a scale STANDARD_DEVIATION 17.7 • n=4 Participants
Patient Health Questionnaire-2 (PHQ-2)	1.9 units on a scale STANDARD_DEVIATION 1.7 • n=5 Participants	1.9 units on a scale STANDARD_DEVIATION 1.8 • n=7 Participants	1.7 units on a scale STANDARD_DEVIATION 1.7 • n=5 Participants	1.8 units on a scale STANDARD_DEVIATION 1.7 • n=4 Participants

PRIMARY outcome

Timeframe: From baseline to day 30

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The primary outcome for this study will be self-reported pain interference using Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) version 8a. The pain interference scale measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5) with a raw score calculated by a sum of the 8 items ranging from 8 to 40. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Day 30 - baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain interference).

Outcome measures

Measure	Distraction-Based VR n=108 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=110 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=114 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) at Day 30	-1.15 units on a scale Standard Deviation 6.63	-1.86 units on a scale Standard Deviation 5.06	-1.67 units on a scale Standard Deviation 5.93

SECONDARY outcome

Timeframe: From baseline to day 60, from baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

One of the secondary outcomes for this study will be self-reported pain interference (PI) using Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) version 8a. The pain interference scale measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5), with a raw score calculated by a sum of the 8 items ranging from 8 to 40. Results are linked to a T-Score to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Day 60 - baseline and Day 90 - baseline, therefore a negative difference corresponds to improvement of symptoms (reduced PI)

Outcome measures

Measure	Distraction-Based VR n=127 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=127 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=131 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) at Day 60 and Day 90 Day 60 - baseline	-1.32 units on a scale Standard Deviation 6.71	-2.41 units on a scale Standard Deviation 6.18	-2.79 units on a scale Standard Deviation 7.73
Change From Baseline in Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) at Day 60 and Day 90 Day 90 - baseline	-1.45 units on a scale Standard Deviation 6.43	-2.79 units on a scale Standard Deviation 5.23	-3.51 units on a scale Standard Deviation 7.15

SECONDARY outcome

Timeframe: From baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants. Missing data was accounted for in the overall number of participants analyzed.

The outcome for this study will be self-reported pain catastrophizing using the Pain Catastrophizing Survey Short Form 6 (PCS SF-6).

Pain catastrophizing is a negative mental set regarding actual or anticipated pain, and includes aspects of rumination, magnification, and sense of helplessness. PCS is a 6-item short form survey that measures rates of high catastrophizing as defined by a score of ≥7. Items are rated on a 5-point Likert scale from "not at all" (0) to "all the time" (4) with a raw score calculated by a sum of the 6 items ranging from 0 to 24.

The scale is positively scored, where higher scores indicate greater levels of pain catastrophizing. The difference from baseline is reported as Day 90 - baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain catastrophizing).

Outcome measures

Measure	Distraction-Based VR n=103 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=106 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=108 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Pain Catastrophizing Survey Short Form 6 (PCS SF-6) at Day 90.	-1.38 units on a scale Standard Deviation 4.69	-3.04 units on a scale Standard Deviation 4.59	-3.27 units on a scale Standard Deviation 4.84

SECONDARY outcome

Timeframe: From baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The primary outcome for this study will be self-reported anxiety using Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety version 4. This scale assesses self-reported perceptions of fear, anxious misery (worry, dread), hyperarousal, and somatic symptoms related to arousal. Items are rated Items are rated on a 5-point Likert scale from "never" (1) to "always" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-Anxiety is positively scored, where higher scores indicate worse anxiety. The difference from baseline is reported as Day 90 - baseline, therefore a negative difference corresponds to improvement of symptoms (reduced anxiety).

Outcome measures

Measure	Distraction-Based VR n=102 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=106 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=109 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Day 90	-1.89 units on a scale Standard Deviation 9.14	-2.88 units on a scale Standard Deviation 9.03	-1.97 units on a scale Standard Deviation 6.95

SECONDARY outcome

Timeframe: From baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The secondary outcome for this study will be self-reported Sleep Disturbance using Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance version 6a. This scale assesses self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This includes perceived difficulties and concerns with getting to sleep or staying asleep, as well as perceptions of the adequacy of and satisfaction with sleep.

Items are rated on a 5-point Likert scale from "not at all" (1) and "very much" (5), with a raw score calculated by a sum of the 6 items ranging from 6 to 30. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-Sleep Disturbance is positively scored, where higher scores indicate worse sleep disturbance. The negative difference from baseline corresponds to improvement of symptoms (reduced sleep disturbance).

Outcome measures

Measure	Distraction-Based VR n=102 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=103 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=109 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance to Day 90	-2.08 units on a scale Standard Deviation 7.27	-2.44 units on a scale Standard Deviation 7.14	-2.76 units on a scale Standard Deviation 7.36

SECONDARY outcome

Timeframe: From baseline to end of treatment at day 90

Population: Responses marked as "Not sure" or missing were excluded from the number analyzed.

The secondary outcome for the this study is the change from study baseline to Day 90 in the frequency of self-reported daily opioid use. Participants were asked at baseline and Day 90 "Are you currently taking an opioid pain medication on a daily basis? Yes, No, or Not sure"

The number of "Yes" responses and the total number of responses is reported.

Outcome measures

Measure	Distraction-Based VR n=127 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=127 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=131 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline to Day 90 in Weekly Average Opioid Usage Baseline	41 Participants	36 Participants	40 Participants
Change From Baseline to Day 90 in Weekly Average Opioid Usage Day 90	26 Participants	26 Participants	30 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The exploratory outcome for this study will be self-reported physical function using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function 6b. The 6-item PROMIS Physical Function scale measures measures self-reported functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living.

Items are rated on a 5-point Likert scale from "Cannot do" (1) to "Not at all" (5), with a raw score calculated by a sum of the 6 items ranging from 6 to 30.Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-Physical Function is positively scored, where higher T-scores indicate better physical function. The difference from baseline is reported as Day 90 - baseline, with positive differences indicating better physical function.

Outcome measures

Measure	Distraction-Based VR n=103 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=106 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=108 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function 6b at Day 90	0.74 units on a scale Standard Deviation 4.14	1.56 units on a scale Standard Deviation 4.56	1.65 units on a scale Standard Deviation 5.16

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The exploratory outcome for this study will be self-reported depression using Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 4 scale. The 4-item PROMIS Depression scale measures self-reported negative mood (sadness, guilt), views of self (self-criticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). Items are rated on a 5-point Likert scale from "never" (1) to "always" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10).

PROMIS-PI is positively scored, where higher scores indicate more severe depression. The negative difference from baseline corresponds to improvement of symptoms (reduced depression symptoms).

Outcome measures

Measure	Distraction-Based VR n=101 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=106 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=108 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 4 at Day 90	-2.02 units on a scale Standard Deviation 7.23	-2.14 units on a scale Standard Deviation 7.37	-1.60 units on a scale Standard Deviation 7.68

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to end of treatment at day 90

The change in average daily steps, as measured by FitBit, is an exploratory endpoint to measure the change in daily physical activity of study participants throughout the duration of study participation. For example, higher number of steps across individuals may indicate greater physical activity, and increasing number of steps throughout the study may indicate improving physical activity.

Data from Fitbit devices were aggregated by Fitabase during a designated window of enrollment. Daily steps were averaged over 7-day periods account for variation in Fitbit adherence, i.e. wearing the device. The average of daily steps taken over the first week of study participation is used as the baseline measurement because Fitbit devices were provisioned to participants after baseline measurements were recorded (e.g. start of treatment). Similarly, an average of daily steps recorded over the final seven days of treatment (to day 90) were measured.

Outcome measures

Measure	Distraction-Based VR n=44 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=52 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=46 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Biometric Data From Fitbit Charge 4 - Change in Average Daily Steps	204.59 steps per day Standard Deviation 2980.20	-810.86 steps per day Standard Deviation 3810.49	156.66 steps per day Standard Deviation 2370.43

OTHER_PRE_SPECIFIED outcome

Timeframe: From day 1 to end of treatment at day 90

The change in average sleep score, as measured by FitBit, is an exploratory endpoint to measure the change of sleep quality throughout the duration of study participation. A higher change in sleep score may indicate improvement in the quality of sleep.

Fitbit calculates sleep score using an algorithm which takes into account heart rate, total time asleep, and stages of sleep. Sleep scores range from 0-100, with the following categories:

Excellent: 90-100 Good: 80-89 Fair: 60-79 Poor: Less than 60

The average score ranges from 72 to 83. Data from Fitbit devices were aggregated by Fitabase during a designated window of enrollment. Sleep scores were averaged over 7-day periods account for variation in Fitbit adherence, i.e. wearing the device. The average of sleep scores recorded over the first week of study participation is used as the baseline. Similarly, an average of sleep scores recorded over the final seven days of treatment (to day 90) was measured.

Outcome measures

Measure	Distraction-Based VR n=30 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=41 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=31 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Biometric Data From Fitbit Charge 4 - Change in Average Sleep Score	0.34 units on a scale Standard Deviation 2.94	-1.17 units on a scale Standard Deviation 7.69	-0.61 units on a scale Standard Deviation 3.40

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured at end of treatment at day 90

Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants across all three arms. Missing data was accounted for in the overall number of participants analyzed.

The overall effect of the treatment from study baseline to Day 90, measured by the Patients' Global Impression of Change (PGIC) is an exploratory endpoint to assess the efficacy of Skills-based and Distraction VR. This scale measures self-reported belief regarding efficacy of treatment.

At Day 90, participants are asked "Since the start of the study, my overall pain is..." with responses on a 7-point Likert scale from "Very much improved" (1) to "Very much worse" (7). Based on the PGIC assessment, a dichotomous scale of "Yes" or "No" was derived. A favorable response of 1-4 on the PGIC indicates "Yes, significant improvement occurred over the course of the study". An unfavorable response of 5-7 indicates "No, significant improvement did not occur over the course of the study".

Number of participants who scored between 1-4, therefore indicating a significant improvement in their pain levels over the course of the study ("Number of participants with "Yes"), are reported below.

Outcome measures

Measure	Distraction-Based VR n=103 Participants EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=106 Participants EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=109 Participants EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Change in Overall Effect of Treatment From Baseline to Day 90 Measured by Patient's Global Impression of Change (PGIC)	53 Participants	59 Participants	68 Participants

Adverse Events

Distraction-Based VR

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Sham VR

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Skills-Based VR

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Distraction-Based VR n=127 participants at risk EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=127 participants at risk EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=131 participants at risk EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Hepatobiliary disorders Cholelithiasis	0.79% 1/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Cardiac disorders Cardiac Arrest and Sepsis	0.79% 1/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Infections and infestations Unexpected fall and fever	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Skin and subcutaneous tissue disorders Hand Infection	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Musculoskeletal and connective tissue disorders Acute-on-chronic Low Back Pain	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Psychiatric disorders Confusion	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Surgical and medical procedures Cervical fusion	0.79% 1/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.

Other adverse events

Measure	Distraction-Based VR n=127 participants at risk EaseVRx-Distraction has the same number of experiences, the same approximate duration of experiences, and the identical user interface as EaseVRx, with a linear prescribed sequence of experiences. The key difference is that instead of offering a variety of VR experiences including education, games, and breath biofeedback, EaseVRx Distraction only includes 360-degree videos - which are also present in EaseVRx. This is intended to remove the effect of education and skills-based training, while preserving the immersive experience of 360- degree VR. Distraction-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Distraction software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Sham VR n=127 participants at risk EaseVRx-Sham software includes 2D nature footage accompanied by neutral music that is selected to be neither relaxing nor distracting, rather than 360-degree, 3D, interactive content specially selected for efficacy. The experience of using EaseVRx-Sham is similar to watching a large-screen TV, but it is not interactive or immersive. EaseVRx Sham has the same number and duration of experiences as EaseVRx, and the functionality of the user interface used to access the experiences is the same. Modifications were made to the appearance of the user interface in order to remove aspects that were added for therapeutic benefit. Sham VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx-Sham software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.	Skills-Based VR n=131 participants at risk EaseVRx+ incorporates the evidence-based principles of CBT, mindful meditation, and physiologic biofeedback therapy using embedded biometric sensors. It combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward living better with chronic pain. The standardized, prescriptive, and reproducible 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. EaseVRx+ also features an on-demand library, allowing users to access any of the unique video sessions as needed. Skills-Based VR: Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html Activity Tracker: Participants among all arms were given the option to passively wear a Fitbit Charge 4 throughout their 90-day study enrollment period. The Fitbit collected biometric data such as daily steps, heart rate, hours of sleep, stages of sleep, and sleep efficiency.
Injury, poisoning and procedural complications Facial Injury Aggravation	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Skin and subcutaneous tissue disorders Skin Allergic Reaction	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	1.6% 2/127 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Psychiatric disorders Anxiety	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	1.5% 2/131 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Eye disorders Blurry Vision	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Eye disorders Corneal Irritation	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Product Issues Cybersickness	0.79% 1/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	6.1% 8/131 • Number of events 8 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Musculoskeletal and connective tissue disorders Neck Pain	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	2.4% 3/127 • Number of events 3 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	6.1% 8/131 • Number of events 13 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Product Issues Discomfort	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Ear and labyrinth disorders Dizziness	3.1% 4/127 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	3.1% 4/131 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Eye disorders Eye Hemorrhage	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Eye disorders Eye Strain	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	2.4% 3/127 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	3.1% 4/131 • Number of events 5 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Difficulty Focusing	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Face Pain	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Headache	1.6% 2/127 • Number of events 3 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	3.1% 4/131 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Gastrointestinal disorders Nausea	3.1% 4/127 • Number of events 5 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	2.4% 3/127 • Number of events 4 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	3.8% 5/131 • Number of events 6 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Cardiac disorders Heart Palpitations	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Infections and infestations Flu	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Insomnia	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Ear and labyrinth disorders Lightheadedness	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Migraines	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 6 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Ear and labyrinth disorders Motion Sickness	1.6% 2/127 • Number of events 7 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Musculoskeletal and connective tissue disorders Upper back pain	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
General disorders Bacterial Infection	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Skin and subcutaneous tissue disorders Skin irritation	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Nervous system disorders Vertigo	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	1.6% 2/127 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.76% 1/131 • Number of events 2 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.
Musculoskeletal and connective tissue disorders Knee Injury	0.79% 1/127 • Number of events 1 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/127 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.	0.00% 0/131 • Adverse event data were collected during participants' 12-week follow-up period. Adverse events were collected primarily by a weekly adverse event assessment questionnaire, and events were also reported if participants indicated an adverse event during communications with study team and via other study free-text responses. Adverse events were considered moderate if medical intervention, such as use of a medication or an outpatient visit to a medical professional, occurred. Events were considered severe if visits with medical professionals involved an overnight stay.

Additional Information

Samuel Eberlein

Cedars-Sinai Medical Center

Phone: 310-423-6721

Email: samuel.eberlein@cshs.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place