Trial Outcomes & Findings for Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase (NCT NCT02874534)

Last Updated: 2020-04-24

Results Overview

Change due to BATA, relative to MBCT, from baseline in right caudate nucleus activation during the anticipation phase of the Monetary Incentive Delay (MID) task assessed by Functional Magnetic Resonance Imaging (fMRI). The BOLD (Blood Oxygen Level-Dependent signal change is expressed as a z-score that represents the magnitude of change relative to baseline. A score of 0 would correspond to no change, and a score of 1 would represent 1 standard deviation of change. The difference in z-scores between the BATA and the MBCT groups reflects the difference in change in fMRI responses between the two treated groups. Thus even a score of 0 in the BATA group may reflect greater change than observed in the MBCT group if change in the MBCT group is negative.

Recruitment status

COMPLETED

Study phase

Target enrollment

57 participants

Primary outcome timeframe

Baseline, 15 weeks

Results posted on

2020-04-24

Participant Flow

Participant milestones

Participant milestones
Measure	Behavioral Activation Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment Behavioral Activation Treatment for Anhedonia (BATA) will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Overall Study STARTED	31	26
Overall Study COMPLETED	23	15
Overall Study NOT COMPLETED	8	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Behavioral Activation Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment Behavioral Activation Treatment for Anhedonia (BATA) will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Overall Study Withdrawal by Subject	5	8
Overall Study Lost to Follow-up	2	2
Overall Study Ongoing in study	1	1

Baseline Characteristics

Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Behavioral Activation n=31 Participants Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment n=26 Participants BATA will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.	Total n=57 Participants Total of all reporting groups
Age, Continuous	27.61 years STANDARD_DEVIATION 8.47 • n=5 Participants	33.35 years STANDARD_DEVIATION 9.25 • n=7 Participants	30.23 years STANDARD_DEVIATION 9.22 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants	26 Participants n=7 Participants	57 Participants n=5 Participants
SHAPS	37.61 units on a scale STANDARD_DEVIATION 4.38 • n=5 Participants	38.00 units on a scale STANDARD_DEVIATION 5.25 • n=7 Participants	37.79 units on a scale STANDARD_DEVIATION 4.76 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 15 weeks

Population: The fMRI data quality for one participant was inadequate and was excluded from the analysis.

Outcome measures

Outcome measures
Measure	Behavioral Activation n=22 Participants Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment n=15 Participants BATA will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Change From Baseline to Week 15 in Neural Activation	0.0075 Z-score Standard Deviation 0.23	-0.1059 Z-score Standard Deviation 0.21

SECONDARY outcome

Timeframe: Baseline, 15 weeks

Population: The fMRI data quality for one participant was inadequate and was excluded from the analysis.

The Snaith-Hamilton Pleasure Scale (SHAPS), used to assess hedonic capacity. The sum of the 14 items scores ranges from 0 to 56. A higher score represents more anhedonic symptoms. The below means represent change in units on the Snaith-Hamilton Pleasure Scale.

Outcome measures

Outcome measures
Measure	Behavioral Activation n=22 Participants Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment n=15 Participants BATA will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Change From Baseline to Week 15 in Snaith-Hamilton Pleasure Scale Score	8.0 units on a scale Standard Deviation 4.87	9.3 units on a scale Standard Deviation 7.6

Adverse Events

Behavioral Activation

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Mindfulness Treatment

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gabriel S. Dichter, PhD

University of North Carolina at Chapel Hill

Phone: 9194450132

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Behavioral Activation n=31 participants at risk Treatment will consist of 15 weekly 45-minute sessions. Session 1 provides orientation and psychoeducation on anhedonia, and activity monitoring is introduced. Sessions 2-3 include structured values assessments of 10 life areas to enhance motivation for sustained behavior change and to clarify goals. Following goals clarification, an activity hierarchy is developed, establishing a set of idiographic behavioral targets across life areas prioritized by ease of implementation to scaffold task engagement during the course of treatment. Behavioral Activation: Treatment will consist of 15 weekly 45-minute sessions.	Mindfulness Treatment n=26 participants at risk BATA will be compared to mindfulness based cognitive therapy (MBCT), chosen because its mechanisms of action are hypothesized to impact different brain mechanisms than BATA. Mindfulness is nonjudgmentally bringing awareness and acceptance to one's present-moment experience. MBCT will be administered in an individual format. The MBCT protocol will be modeled on the session outlines presented in Wahbeh et al., 2014. Treatment will be compromised of 15 weekly 45-minute sessions. Mindfulness Treatment: Treatment will consist of 15 weekly 45-minute sessions.
Musculoskeletal and connective tissue disorders Back Pain	6.5% 2/31 • Number of events 3 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Skin and subcutaneous tissue disorders Burns on right forearm	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Cold Symptoms	6.5% 2/31 • Number of events 2 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Metabolism and nutrition disorders Decreased appetite	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Endocrine disorders Elevated TSH	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Flu	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Musculoskeletal and connective tissue disorders Hip Pain	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Cardiac disorders Hypertension	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Eye disorders Intermittent eye twitching	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Pneumonia	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Skin and subcutaneous tissue disorders Scalp Acne	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Sinus Infection	6.5% 2/31 • Number of events 2 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Psychiatric disorders Suicidal Ideation	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Skin and subcutaneous tissue disorders Telogen Effluvium	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Upper respiratory infection	3.2% 1/31 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	0.00% 0/26 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Cardiac disorders Presyncopal Episode	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Musculoskeletal and connective tissue disorders Broken Collar Bone	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Infections and infestations Streptococcal pharyngitis	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.
Musculoskeletal and connective tissue disorders Worsening arthritis	0.00% 0/31 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.	3.8% 1/26 • Number of events 1 • From initial assessment through post treatment scan, a total of approximately 3 to 5 months. Study team members (e.g., study coordinator, study therapists) asked participants at each visit following the initial appointment if any adverse events or changes in health were experienced since the last visit. Adverse Events were assessed by a trained study coordinator, study therapist, or other approved study team member, and discussed at the weekly research staff meetings.