Trial Outcomes & Findings for STEM-Parkinson's Disease (NCT NCT04797611)

NCT ID: NCT04797611

Last Updated: 2025-05-13

Results Overview

The MDS-NMS is a 52-item rater-administered scale used to assess a wide range of non-motor symptoms in Parkinson's disease. It measures both frequency (0/never to 4/ \>51% of the time) and severity (0/not present to 4/major distress or disturbance) of 13 domains (depression, anxiety, apathy, psychosis, impulse control/related disorders, cognition, orthostatic hypotension, urinary, sexual, gastrointestinal, sleep/wakefulness, pain, and other). Each question is scored by multiplying frequency x severity. All question scores for each domain are summed, and the scores for each domain are summed to provide the Total Score (range = 0-832) with the higher score indicating greater non-motor symptom burden. The higher the total score, the more progressed (i.e., worse) is the disease state. The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 188 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2025-05-13

Participant Flow

Participant milestones

Measure	Active: Investigational Treatment 1 Investigational treatment mode (stimulation pattern) 1 - Twice daily, \~ 19-minute, active time-varying caloric vestibular stimulation (tvCVS) treatments.	Passive: Investigational Treatment 2 Investigational treatment mode (stimulation pattern) 2. Twice daily, \~ 19-minute, passive, time-varying caloric vestibular stimulation (tvCVS) treatments.
Overall Study STARTED	96	92
Overall Study COMPLETED	86	85
Overall Study NOT COMPLETED	10	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

1 participant had a missing value for LEDD.

Baseline characteristics by cohort

Measure	Investigational Treatment 1 n=96 Participants Investigational treatment mode (stimulation pattern) 1	Investigational Treatment 2 n=92 Participants Investigational treatment mode (stimulation pattern) 2	Total n=188 Participants Total of all reporting groups
Age, Continuous	68.4 years STANDARD_DEVIATION 7.56 • n=96 Participants	69.1 years STANDARD_DEVIATION 7.75 • n=92 Participants	68.7 years STANDARD_DEVIATION 7.64 • n=188 Participants
Sex: Female, Male Female	32 Participants n=96 Participants	24 Participants n=92 Participants	56 Participants n=188 Participants
Sex: Female, Male Male	64 Participants n=96 Participants	68 Participants n=92 Participants	132 Participants n=188 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=96 Participants	0 Participants n=92 Participants	0 Participants n=188 Participants
Race (NIH/OMB) Asian	1 Participants n=96 Participants	6 Participants n=92 Participants	7 Participants n=188 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=96 Participants	0 Participants n=92 Participants	0 Participants n=188 Participants
Race (NIH/OMB) Black or African American	2 Participants n=96 Participants	2 Participants n=92 Participants	4 Participants n=188 Participants
Race (NIH/OMB) White	90 Participants n=96 Participants	83 Participants n=92 Participants	173 Participants n=188 Participants
Race (NIH/OMB) More than one race	0 Participants n=96 Participants	0 Participants n=92 Participants	0 Participants n=188 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=96 Participants	1 Participants n=92 Participants	4 Participants n=188 Participants
Years Since Parkinson's Diagnosis	6.9 years STANDARD_DEVIATION 3.53 • n=96 Participants	7.1 years STANDARD_DEVIATION 5.02 • n=92 Participants	7.0 years STANDARD_DEVIATION 4.32 • n=188 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=96 Participants	1 Participants n=92 Participants	4 Participants n=188 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	93 Participants n=96 Participants	91 Participants n=92 Participants	184 Participants n=188 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=96 Participants	0 Participants n=92 Participants	0 Participants n=188 Participants
Levodopa Equivalent Daily Dose (LEDD)	783.3 milligrams of Levodopa STANDARD_DEVIATION 481.21 • n=96 Participants • 1 participant had a missing value for LEDD.	792.2 milligrams of Levodopa STANDARD_DEVIATION 568.89 • n=91 Participants • 1 participant had a missing value for LEDD.	787.6 milligrams of Levodopa STANDARD_DEVIATION 524.30 • n=187 Participants • 1 participant had a missing value for LEDD.
Years of Formal Education < = 12 Years	4 Participants n=96 Participants	2 Participants n=92 Participants	6 Participants n=188 Participants
Years of Formal Education > 12 years	92 Participants n=96 Participants	90 Participants n=92 Participants	182 Participants n=188 Participants

PRIMARY outcome

Timeframe: 3 months

Population: Only the participants with data for the end of treatment visit were included in the overall number of participants analyzed.

The MDS-NMS is a 52-item rater-administered scale used to assess a wide range of non-motor symptoms in Parkinson's disease. It measures both frequency (0/never to 4/ >51% of the time) and severity (0/not present to 4/major distress or disturbance) of 13 domains (depression, anxiety, apathy, psychosis, impulse control/related disorders, cognition, orthostatic hypotension, urinary, sexual, gastrointestinal, sleep/wakefulness, pain, and other). Each question is scored by multiplying frequency x severity. All question scores for each domain are summed, and the scores for each domain are summed to provide the Total Score (range = 0-832) with the higher score indicating greater non-motor symptom burden. The higher the total score, the more progressed (i.e., worse) is the disease state.

The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening.

Outcome measures

Measure	Active: Investigational Treatment 1 n=89 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=85 Participants Investigational treatment mode (stimulation pattern) 2
Change in The International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) Total Score	-21.2 score on a scale Standard Deviation 41.62	-18.3 score on a scale Standard Deviation 47.33

SECONDARY outcome

Timeframe: 3 months

Population: The number of participants includes only those who had both baseline and end of treatment data. Many participants did not complete the patient-reported outcomes and, therefore, had missing MDS-UPDRS Part II scores, which is a component of this scale. In other cases, MDS-UPDRS III scores were missing, because participants performed the MDS-UPDRS III virtually and assessors could not assess.

The MDS-UPDRS evaluates motor (Parts 1 and III) and non-motor (Part II) experiences and complications of Parkinson's disease (PD) to characterizes the extent and burden of disease. Each question has five response options linked to accepted clinical terms: (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe)/evaluations and are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), and Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points). The Combined Score is the sum of the points for all three Parts and ranges from 0 to 236. The higher the score, the more progressed (i.e., worse) is the disease state.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=72 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=68 Participants Investigational treatment mode (stimulation pattern) 2
Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Parts I, II, and III Combined Score	-3.8 score on a scale Standard Deviation 12.05	-1.7 score on a scale Standard Deviation 12.89

SECONDARY outcome

Timeframe: 3 months

Population: The overall number of participants includes only those who completed this patient reported outcome at their end of treatment visit. Those skipped/not completed by the participant are not included.

The MDS-UPDRS Part II is a 13-item patient-reported assessment of motor aspects of experiences of daily living. Scores range between 0-52, with the higher score indicating greater impairment to activities of daily living.

The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. The more negative the change score, the greater the improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=79 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=75 Participants Investigational treatment mode (stimulation pattern) 2
Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II	-0.3 score on a scale Standard Deviation 2.95	0.0 score on a scale Standard Deviation 4.02

SECONDARY outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only randomized participants with non-missing values.

The Clinical Global Impression-Improvement (CGI-I) is a clinician outcome assessment used to assess the extent of clinically meaningful change that has occurred in the patient's illness at day 113 relative to a baseline state (assessed at day 29). Changes in all aspects of Parkinson's disease (e.g., motor symptoms, non-motor symptoms and complications of anti-Parkinsonian medications) are considered. A 0 corresponds to no change, higher magnitude positive values correspond to greater improvements, and higher magnitude negative scores correspond to increased worsening. Scores range from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = no change, 1=minimally improved, 2=much improved, 3=very much improved).

Outcome measures

Measure	Active: Investigational Treatment 1 n=87 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=88 Participants Investigational treatment mode (stimulation pattern) 2
Change From Baseline in the Clinical Global Impression-Improvement (CGI-I)	0.3 score on a scale Standard Deviation 0.98	0.4 score on a scale Standard Deviation 1.04

SECONDARY outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only randomized participants with a non-missing values, who have both baseline and end of treatment data. Analysis only derived from levodopa ON-state scores, if data was collected in the levodopa OFF-state, this was not analyzed. Also if visits were performed virtually the assessor could not perform the full assessment, so total score could not be calculated

The MDS-UPDRS Part III is a 33-item assessment of motor function evaluated by a trained, blinded rater. Each item has five response options linked to accepted clinical terms (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe) for a total scoring range of 0-132. Higher scores indicate more severe motor symptoms.

The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=91 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=88 Participants Investigational treatment mode (stimulation pattern) 2
Change in the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale MDS-UPDRS Part III	-1.1 score on a scale Standard Deviation 9.43	0.7 score on a scale Standard Deviation 8.87

SECONDARY outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only the number of participants with a non-missing values at both baseline and end of treatment visit. As this is a patient reported outcome, it was occasionally missed/skipped at visits.

The PDQ-39 is a 39-item patient reported outcome questionnaire, which assesses Parkinson's disease-specific health related quality over the previous month. It includes 39 questions covering 8 dimensions: mobility (10), activities of daily living (6), emotional well-being (6), stigma (4), social support (3), cognition (4), communication (3), and bodily discomfort (3). Answers range from 0/never to 4/always. Each dimension is scored by summing the scores of each item, dividing that maximum possible score of all items in the dimension, and then multiplying by 100. The overall questionnaire score (the SI score) is the sum of all dimension scores divided by 8. Lower scores reflect better QoL.

The change/difference in scores between the baseline (Days 1 and 29 average) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=79 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=73 Participants Investigational treatment mode (stimulation pattern) 2
Change From in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI)	-3.09 score on a scale Standard Deviation 7.461	-1.72 score on a scale Standard Deviation 7.497

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only participants who completed the assessment at both baseline and end of study visits. Adverse Events that impact motor function/walking/gait or the visit being performed virtually could impact the ability to perform this assessment.

The Mini-BESTest is a 14-item test scored on a 3-level ordinal scale that assesses dynamic balance in terms of anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. Answers to each of the 14 items range from 0/severe difficulty to 2/normal (no difficulty) for a total possible score ranging from 0 to 28 points. The lower the score the more difficulty was encountered. Higher scores reflect more ease in completing the tasks.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates improvement. A negative change in scores indicates worsening.

Outcome measures

Measure	Active: Investigational Treatment 1 n=86 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=83 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Mini-Balance Evaluation Systems Test (Mini BESTest)	0.1 score on a scale Standard Deviation 3.24	0.1 score on a scale Standard Deviation 2.85

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only the number of participants with a non-missing value at their end of treatment visit. Visits performed virtually could not perform this assessment.

The MoCA assesses cognition over 6 domains: Memory, Executive function, Attention, Language, Visuospatial, and Orientation. Points across all 6 domains are summed, and this sum equals the total score (min 0 - max 30). A higher total score indicates better cognitive function; a positive score for difference in points indicates improvement. A total score of 26-30 reflects normal cognition. Mild cognitive impairment is associated with a total score of 18-25. Total scores of 10 - 17 indicate moderate cognitive impairment; a total score less than 10 shows severe cognitive impairment.

The change (difference) in the Montreal Cognitive Assessment (MoCA) total score taken at baseline and, again, at the end of treatment visit is reported. A positive change in scores indicates improvement; whereas, a negative change in scores between baseline and end of treatment indicates worsening.The more positive the change score, the greater the improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=87 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=86 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Montreal Cognitive Assessment (MoCA)	0.0 score on a scale Standard Deviation 2.24	-0.2 score on a scale Standard Deviation 2.65

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The number of participants who performed both baseline and end of treatment visits with non-missing values. Visits performed virtually could not perform this assessment.

The oral SDMT assesses cognition that primarily evaluates processing speed and sustained attention. It involves a substitution task where the test taker pairs specific numbers with given geometric figures using a reference key. The oral version of the test allows responses to be given verbally, making it suitable for individuals with motor disabilities or speech disorders. It is scored based on the number of correct substitutions made. The scoring range for the oral version of the SDMT is from 0 to 110, where the score represents the number of correct substitutions made within 90 seconds and the maximum score is 110 points. A higher score indicates better performance, as it reflects a faster cognitive processing speed.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates improvement. A negative change in scores indicates worsening.

Outcome measures

Measure	Active: Investigational Treatment 1 n=79 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=78 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Oral Symbol Digit Modality Test (Oral SDMT)	-0.5 score on a scale Standard Deviation 7.89	0.4 score on a scale Standard Deviation 6.82

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The number of participants who completed this patient reported outcome at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The PDSS-2 is a patient-completed clinical rating scale that assesses the frequency of sleep disturbances over the past week. Each question is scored between 0 ("never") and 4 ("very often"), and a total score is calculated by summing a patient's responses to each of the 15 questions (minimum 0 to maximum 60). It has three domains: 1) motor problems at night, 2) PD symptoms at night, and 3) disturbed sleep. Total score ranges from 0 to 60, with the score of each domain ranging from 0 to 20. Higher scores represent more nighttime sleep-related problems.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=75 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=65 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Parkinson's Disease Sleep Scale 2 (PDSS 2)	-1.1 score on a scale Standard Deviation 7.88	0.7 score on a scale Standard Deviation 6.46

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The number of participants who completed this patient reported outcome at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The ESS is a questionnaire used to assess daytime sleepiness. The scale consists of eight questions where respondents rate their likelihood of falling asleep in various situations on a scale from 0 to 3, with 0 indicating no chance and 3 indicating a high likelihood. The total score ranges from 0 to 24. Results from 0 to 10 show average (normal) daytime sleepiness; a result under 10 may not be cause for concern or it could identify you have trouble sleeping (insomnia). A result from 11 to 24 indicates excessive (abnormal) daytime sleepiness (10-14 is mild, 15-17 is moderate, and 18 or higher is severe).

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=75 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=67 Participants Investigational treatment mode (stimulation pattern) 2
Change in Epworth Sleepiness Scale (ESS)	-0.3 score on a scale Standard Deviation 3.10	0.0 score on a scale Standard Deviation 3.44

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The number of participants who completed this patient reported outcome at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The PAS is a 12-item observer or patient-rated scale designed to measure the severity of anxiety symptoms in patients with Parkinson's disease (PD). It includes three subscales that evaluate persistent anxiety (1-5), anxiety episodes (6-9), and avoidance behavior (10-12). Each item is scored on a 5-point Likert scale, where a score of "0" indicates "not" or "never," and a score of "4" indicates "severe" or "almost always." The total score for each subscale is calculated by summing the scores of the respective items. The maximum score for the entire scale is 48 points. A higher score indicates more severe anxiety symptoms.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=74 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=69 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Parkinson Anxiety Scale (PAS)	-0.9 score on a scale Standard Deviation 5.24	-0.9 score on a scale Standard Deviation 4.75

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of paticipants analyzed includes only the participants who completed this measure at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The FACIT-Fatigue assesses fatigue-related symptoms and their impact on daily functioning. The scale includes a five-item symptom subscale and an eight-item impact subscale, totaling 13 items.

For each item, level of fatigue is rated as 0 (Not at all) to 4 (Very much so). To score the FACIT-Fatigue, all items' ratings are summed to create a single fatigue score with a range from 0 to 52. Higher scores represent less fatigue, while lower scores indicate more fatigue.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates improvement. A negative change in scores indicates worsening.

Outcome measures

Measure	Active: Investigational Treatment 1 n=76 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=68 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue)	1.4 score on a scale Standard Deviation 6.02	1.3 score on a scale Standard Deviation 8.02

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only participants who completed this measure at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The GDS-15 is a short, self-report questionnaire to identify depression in older adults. It consists of 15 items that assess mental health based on feelings over the past week. 1 point is given for any answer indicating depression; 0 is given for any answer not indicating depression. The total score is the sum of all items and points given and ranges from 0-15, with higher scores indicating more depression.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=74 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=67 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Geriatric Depression Scale-15 (GDS-15)	-0.1 score on a scale Standard Deviation 2.47	-0.1 score on a scale Standard Deviation 1.78

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: Only participants with non-missing data at both baseline and end of treatment visits for this measure were included in the analysis population.

The MDS-NMS NMF is a rater completed subscale that assesses the degree of change (0/no change to 4/large change) in non-motor symptoms in relation to the timing of anti-parkinsonian medications across 8 domains (depression, anxiety, thinking/cognitive abilities, bladder symptoms, restlessness, pain, fatigue, and excessive sweating). The degree of change provided for each of the 8 domains are summed. This sum is then multiplied by the time spent in non-motor "off" state (1/Rarely to 4/Majority of time) to obtain the MDS-NMS NMF Total Score.

Total possible scores for this scale measure range from 0 to 334. The higher the total score, the more progressed (i.e., worse) is the disease state.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=86 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=83 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) Non-Motor Fluctuations (NMF) Subscale Score	0.6 score on a scale Standard Deviation 10.61	-1.9 score on a scale Standard Deviation 13.36

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only participants who completed this measure at both baseline and end of treatment visits.

The UPDRS measures the severity and progression of Parkinson disease. Part IV assesses motor complications and is scored with yes and no ratings. Scores range: 0-24. Higher scores are worse; 4 and below is mild while 13 and above is severe.

Change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement. The more negative the change score, the greater the improvement

Outcome measures

Measure	Active: Investigational Treatment 1 n=88 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=88 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV	-0.6 score on a scale Standard Deviation 2.01	0.0 score on a scale Standard Deviation 2.16

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only participants who completed this measure at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing.

The ZBI is a 22-item questionnaire designed to measure the extent to which a caregiver perceives their level of burden because of caretaking. Each item on the interview is a statement which the caregiver is asked to endorse using a 5-point scale, ranging from 0 (Never) to 4 (Nearly Always). Total scores are obtained by summing all items endorsed. Scores are interpreted as follows: 0 to 21 indicates little or no burden, 21 to 40 indicates mild to moderate burden, 41 to 60 indicates moderate to severe burden, and 61 to 88 indicates severe burden.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=81 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=78 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Zarit Burden Interview (ZBI)	19.6 score on a scale Standard Deviation 11.74	17.9 score on a scale Standard Deviation 11.08

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only participants who completed this measure at both baseline and end of treatment. As this is a patient reported outcome, is was occasionally skipped/missing also visits performed virtually could not perform this assessment.

The PRO-PD is a self-rating, 32 item, visual analog scale (VAS) that assesses severity of PD symptoms. Each item evaluates a common PD symptom, covering both motor and non-motor symptoms, and is scored on a range from 0 ("no problem") to 100 ("extreme problem") points. The scores for all items are summed to obtain a total score that can range from 0 to 3200. Higher scores indicate more severe symptoms or greater impact on the patient's life.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=86 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=82 Participants Investigational treatment mode (stimulation pattern) 2
Change in the Patient Reported Outcome - Parkinson's Disease (PRO-PD)	-51.3 score on a scale Standard Deviation 239.77	10.3 score on a scale Standard Deviation 311.63

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only those who completed this measure at both baseline and end of treatment visits.

This single-item clinical outcome scale assesses the functional status of individuals with Parkinson's Disease (PD). It evaluates their ability to perform daily activities, ranging from complete independence to complete dependence, with scores given in 10% increments from 100% (completely independent) to 0% (bedridden). The higher the score the more independent the participant is.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates improvement. A negative change in scores indicates worsening.

Outcome measures

Measure	Active: Investigational Treatment 1 n=89 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=88 Participants Investigational treatment mode (stimulation pattern) 2
Change in The Modified Schwab and England Activities of Daily Living Scale	-0.8 percentage of independence Standard Deviation 15.13	0.7 percentage of independence Standard Deviation 10.10

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only those who completed this measure at baseline and end of treatment. Data was to be collected on an smartphone application downloaded on the participants personal phone; however, not all smartphones could use the application.

Encephalog is an app through which the 3 Meter TUG Test can be run to evaluate the risk of falls in adults. The patient sits in with their back against the chair back. At "go," the patient rises from the chair, walks 3 meters at a comfortable/safe pace, turns, walks back to the chair, and sits. Timing begins at "go" and stops when reseated. The test measures in seconds. Scores indicate levels of mobility and fall risk; the higher the score (i.e., the longer it takes), the worse the functional mobility and greater the risk of falls: 10 seconds or less - normal mobility; 11-20 seconds - normal limits for frail/elderly/disabled patients; 20 seconds or more - need assistance, further examination and intervention; 30 seconds or more - significant mobility issue.) The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=43 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=37 Participants Investigational treatment mode (stimulation pattern) 2
Change in EncephaLog™ 3 Meter Timed Up and Go (TUG) Test	-0.135 seconds Standard Deviation 4.9007	-0.675 seconds Standard Deviation 3.4686

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only those who completed this test at both baseline and end of treatment. This data was collected on an smartphone application downloaded on the participants personal phone, however, not all smartphones could use the application.

EncephaLog™ is a smartphone app through which the finger tapping test is conducted. The finger tapping test provides a quantitative measure of bradykinesia. A participant taps the phone as quickly as possible for 10 seconds with their index finger. Both left and right hand are tested. Scoring counts the number of finger taps in 10 seconds. The higher the score the more severe the symptoms.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement. The more positive the change score, the greater the improvement

Outcome measures

Measure	Active: Investigational Treatment 1 n=52 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=52 Participants Investigational treatment mode (stimulation pattern) 2
Change in EncephaLog™ Finger Tapping Test	5.9 # of finger taps in 10 seconds Standard Deviation 12.15	4.5 # of finger taps in 10 seconds Standard Deviation 14.98

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: This data was collected on an smartphone application downloaded on the participants personal phone. Not all smartphones could use the application.

EncephaLog™ is a smartphone app that measures gait and that provides indication of risk of falls in adults. The patient sits in the chair with his/her back against the chair back. On the command "go," the patient rises from the chair, walks 10 meters at a comfortable and safe pace, turns, walks back to the chair and sits down. Timing begins at the instruction "go" and stops when the patient is seated. Shorter times indicate less dysfunction.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=49 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=48 Participants Investigational treatment mode (stimulation pattern) 2
Change in EncephaLog™ 10 Meter Timed Up and Go (TUG) Test	0.37 seconds Standard Deviation 2.807	0.02 seconds Standard Deviation 0.310

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: The overall number of participants analyzed includes only those that completed this measure at both baseline and end of treatment visits.

The UPDRS measures the severity and progression of Parkinson disease. Part I assesses Non-Motor Experiences of Daily Living in terms of mentation, behavior, and mood and is scored on a 0-4 rating scale. Total scores range from 0-16 with higher scores indicating more severe symptoms.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=87 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=88 Participants Investigational treatment mode (stimulation pattern) 2
Change in Unified Parkinson's Disease Rating Scale Part I (UPDRS I)	-0.6 score on a scale Standard Deviation 2.13	0.0 score on a scale Standard Deviation 1.81

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: Only participants completed this measure in-person at both baseline and end of treatment visits were included in the overall number of participants analyzed. If the visit was conducted virtually, instead of in-person, this assessment could not be scored.

The Hoehn & Yahr scale is used to describe the progress of Parkinson's disease. Scoring is based on the level/stage of clinical disability described by severity of motor symptoms. Stage 1: Unilateral involvement only, usually with minimal or no functional disability. Stage 1.5: Unilateral and axial involvement. Stage 2: Bilateral involvement without impairment of balance. Stage 2.5: Mild bilateral disease with recovery on pull test. Stage 3: Bilateral disease with mild to moderate disability and impaired postural reflexes; physically independent. Stage 4: Severely disabling disease, still able to walk or stand unassisted. Stage 5: Confinement to bed or wheelchair unless aided. The greater the stage description, the more advanced the disease.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=81 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=79 Participants Investigational treatment mode (stimulation pattern) 2
Change in Hoehn & Yahr (H&Y)	0.0 score on a scale Standard Deviation 0.55	0.0 score on a scale Standard Deviation 0.52

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: Only participants who completed both baseline and end of treatment visits were included in the overall number of participants analyzed.

The MDS-UPDRS evaluates motor and non-motor experiences and complications of Parkinson's disease (PD) by which it characterizes the extent and burden of disease. Part I is a motor subscale of 13 questions. Each question has five response options linked to accepted clinical terms (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe) for a total possible score of 52 possible points.

The higher the total score, the more progressed (i.e., worse) is that motor aspect of the disease.

The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Measure	Active: Investigational Treatment 1 n=87 Participants Investigational treatment mode (stimulation pattern) 1	Passive: Investigational Treatment 2 n=85 Participants Investigational treatment mode (stimulation pattern) 2
Change in International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS I) Score	-1.7 score on a scale Standard Deviation 5.04	-1.8 score on a scale Standard Deviation 4.99

Adverse Events

Investigational Treatment 1

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Investigational Treatment 2

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Investigational Treatment 1 n=96 participants at risk Investigational treatment mode (stimulation pattern) 1 Non-invasive brainstem stimulation: Study participants will self-administer \~19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.	Investigational Treatment 2 n=92 participants at risk Investigational treatment mode (stimulation pattern) 2 Non-invasive brainstem stimulation: Study participants will self-administer \~19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.
Cardiac disorders Acute Myocardial Infarction/NSTEMI	1.0% 1/96 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	0.00% 0/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Gastrointestinal disorders Intestinal perforation	0.00% 0/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	1.1% 1/92 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Renal and urinary disorders Urinary Obstruction	1.0% 1/96 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	0.00% 0/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin Cancer	1.0% 1/96 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	0.00% 0/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Injury, poisoning and procedural complications Fall secondary to NSTEMI	1.0% 1/96 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	0.00% 0/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Vascular disorders Hypotension	1.0% 1/96 • Number of events 1 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	0.00% 0/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.

Other adverse events

Measure	Investigational Treatment 1 n=96 participants at risk Investigational treatment mode (stimulation pattern) 1 Non-invasive brainstem stimulation: Study participants will self-administer \~19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.	Investigational Treatment 2 n=92 participants at risk Investigational treatment mode (stimulation pattern) 2 Non-invasive brainstem stimulation: Study participants will self-administer \~19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.
Infections and infestations COVID-19	6.2% 6/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	7.6% 7/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Infections and infestations Nasopharyngitis	6.2% 6/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	2.2% 2/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Injury, poisoning and procedural complications Fall	8.3% 8/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	12.0% 11/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
General disorders Medical Device site discomfort	5.2% 5/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	4.3% 4/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.
Nervous system disorders Dizziness	7.3% 7/96 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.	3.3% 3/92 • 4 months- from consent to Day 113 Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users, or other persons, whether or not related to the investigational medical device. Adverse Device Effect (ADE): any AE related to the use of an investigational medical device. Serious Adverse Event (SAE): meets the clinicaltrials.gov definition. Serious Adverse Device Effect (SADE): any SAE related the device use.

Additional Information

Robert Black

Scion NeuroStim, Inc

Phone: 919-260-5528

Email: bacllc@earthlink.net

Results disclosure agreements

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