Trial Outcomes & Findings for STEM-PD Open Label Extension (OLE) (NCT NCT04799418)

NCT ID: NCT04799418

Last Updated: 2025-07-03

Results Overview

The primary endpoint is the change in MDS-NMS total score during the first treatment period during the open label extension (OLE) relative to the score at the end of the NCT04797611 randomized controlled trial (RCT) treatment period (day 113) for the passive-active treatment group compared to the change in MDS-NMS total score during the RCT treatment period relative to the pretreatment baseline. The MDS-NMS is 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. 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.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 148 participants
• Primary outcome timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; This OLE: Day 113 to Day 197)
• Results posted on: 2025-07-03

Participant Flow

Participants (active or passive) completing NCT04797611 were eligible to enter this open label extension (OLE) study to receive active devices. NCT04797611 study was completed, however this OLE study terminated early, due to company closure. Incomplete data prevented analysis. Results posted compare the group differences by outcome measure for NCT04797611 passive participants who completed this active OLE (for passive-active only). Active-active outcomes were exploratory and so are not posted.

Participant milestones

Measure	Experimental: Passive-active This group received passive treatment with the study device in a randomized controlled trial (RCT) that immediately preceded this open label extension (OLE ) study during which participants received active (i.e., time-varying caloric vestibular stimulation) treatment.	Experimental: Active-active This group received active (i.e., time-varying caloric vestibular stimulation) treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active treatment. Data obtained from this group was only utilized for exploratory outcome measures.
Overall Study STARTED	69	79
Overall Study Completion of Treatment Period 1	66	76
Overall Study Completion of Follow-Up Period	47	57
Overall Study COMPLETED	41	55
Overall Study NOT COMPLETED	28	24

Reasons for withdrawal

Measure	Experimental: Passive-active This group received passive treatment with the study device in a randomized controlled trial (RCT) that immediately preceded this open label extension (OLE ) study during which participants received active (i.e., time-varying caloric vestibular stimulation) treatment.	Experimental: Active-active This group received active (i.e., time-varying caloric vestibular stimulation) treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active treatment. Data obtained from this group was only utilized for exploratory outcome measures.
Overall Study Death	1	1
Overall Study Lack of Efficacy	14	14
Overall Study Withdrawal by Subject	10	7
Overall Study Adverse Event	3	2

Baseline Characteristics

This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment

Baseline characteristics by cohort

Measure	Experimental: Passive-active n=69 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active (i.e., time-varying caloric vestibular stimulation) treatment.	Experimental: Active-active n=79 Participants This group received active (i.e. time-varying caloric vestibular stimulation) treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active treatment. Data obtained from this group was only utilized for exploratory outcome measures.	Total n=148 Participants Total of all reporting groups
Years of Education < = 12 years of Education	1 Participants n=5 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment	2 Participants n=7 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment	3 Participants n=5 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment
Age, Continuous	68.8 years STANDARD_DEVIATION 7.6 • n=5 Participants	68.5 years STANDARD_DEVIATION 7.5 • n=7 Participants	68.6 years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	27 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	52 Participants n=7 Participants	103 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	5 Participants n=5 Participants	1 Participants n=7 Participants	6 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	76 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Years of Education > 12 Years of Education	68 Participants n=5 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment	77 Participants n=7 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment	145 Participants n=5 Participants • This data is derived from the Montreal Cognitive Assessment, which is performed at interim visits, and not all participants that entered the OLE completed the assessment

PRIMARY outcome

Timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; This OLE: Day 113 to Day 197)

Population: This population received passive treatment during the RCT that preceded this phase of the study and active treatment in this OLE. Only participants who completed the assessments at least once during the pre-treatment baseline period and at both the RCT end of treatment visit and the end of treatment period 1 visit during this OLE are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

The primary endpoint is the change in MDS-NMS total score during the first treatment period during the open label extension (OLE) relative to the score at the end of the NCT04797611 randomized controlled trial (RCT) treatment period (day 113) for the passive-active treatment group compared to the change in MDS-NMS total score during the RCT treatment period relative to the pretreatment baseline. The MDS-NMS is 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. 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.

Outcome measures

Measure	Randomized Controlled Trial (RCT) Passive Treatment n=64 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=64 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in The International Parkinson and Movement Disorder Society - Non-Motor Rating Scale (MDS-NMS) Total Score	-23.12 change in score on a scale from baseline Interval -33.11 to -13.12	3.28 change in score on a scale from baseline Interval -8.18 to 14.74

SECONDARY outcome

Timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197)

Population: This population received passive treatment during the RCT that preceded this OLE study during which they received active treatment. Only participants who completed the assessments at least once during the pre-treatment baseline period and at both the RCT end of treatment visit and the end of treatment period 1 visit during this OLE are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

The MDS-UPDRS Part II is a 13-item patient-reported assessment of activities 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. This secondary endpoint evaluates the change in the MDS-UPDRS Part II score obtained during the first treatment period of this open label extension (OLE) relative to the score obtained at the end of the NCT04797611 randomized controlled trial (RCT) period (day 113).

Outcome measures

Measure	Randomized Controlled Trial (RCT) Passive Treatment n=50 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=50 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II	-0.03 change in score on a scale from baseline Interval -1.11 to 1.05	0.60 change in score on a scale from baseline Interval -0.67 to 1.87

SECONDARY outcome

Timeframe: RCT: from Baseline (Day 29) up to 3 months (Day 113); OLE: from Baseline (Day 29) up to 11 months (Day 365)

Population: This population received passive treatment during the NCT04797611 RCT that preceded the active treatment received in this OLE study. Only participants who completed the assessments at least once during the RCT's pre-treatment baseline period, the RCT's end of treatment visit, and this OLE's end of treatment period 1 visit are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

The CGI-I is a clinician assessment the extent of clinically meaningful change that has occurred in the patient's illness at day 197/365 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	Randomized Controlled Trial (RCT) Passive Treatment n=66 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=66 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 1 - Very Much Improved	0 Participants	0 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 2 - Much Improved	12 Participants	10 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 3 - Minimally Improved	22 Participants	23 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 4 - No Change	23 Participants	17 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 5 - Minimally Worse	7 Participants	11 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 6 - Much Worse	2 Participants	5 Participants
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I) 7 - Very Much Worse	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197)

Population: This population received passive treatment during the RCT that preceded this phase of the study and active treatment in this OLE. Only participants who completed the assessments at least once during the RCT's pre-treatment baseline period and end of treatment visit and who completed the end of treatment period 1 visit during this OLE are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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. This secondary endpoint evaluates the change in MDS-UPDRS Part III score during the first treatment period of this open label extension (OLE) relative to the score at the end of the NCT04797611 randomized controlled trial (RCT) treatment period (day 113) for the passive-active treatment group compared to the change in MDS-UPDRS Part III score during the RCT treatment period relative to the pre-treatment baseline.

Outcome measures

Measure	Randomized Controlled Trial (RCT) Passive Treatment n=58 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=58 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination (MDS-UPDRS Part III)	3.0 change in score on a scale from baseline Interval -3.0 to 7.0	-1.5 change in score on a scale from baseline Interval -8.0 to 7.3

SECONDARY outcome

Timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197

Population: This population received passive treatment during the RCT that preceded this phase of the study and active treatment in this OLE. Only participants who completed the assessments at least once during the pre-treatment baseline period and at both the RCT end of treatment visit and the end of treatment period 1 visit during this OLE are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

The PDQ-39 SI is a 39-item patient-reported quality of life measure that assesses how often people living with PD are affected across 8 dimensions of daily living covering: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items), and bodily discomfort (3 items). Answers for each item 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 total score (the SI score) is the sum of all dimension scores divided by 8 and ranges from 0-100, the higher the total score the greater the health problems).

This endpoint compares the change in the PDQ-39 total score taken at the end of the RCT treatment period to the total score obtained during the OLE's first treatment period.

Outcome measures

Measure	Randomized Controlled Trial (RCT) Passive Treatment n=46 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=46 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI)	-2.20 change in score on a scale from baseline Interval -6.93 to 12.1	0.15 change in score on a scale from baseline Interval -2.68 to 2.6

SECONDARY outcome

Timeframe: 3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197

Population: This population received passive treatment during the RCT that preceded this phase of the study and active treatment in this OLE. Only participants who completed the assessments at least once during the RCT's pre-treatment baseline period and the RCT's end of treatment visit and at the end of this OLE's treatment period 1 visit are included in the results posted. Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

The MDS-UPDRS evaluates motor (Parts I 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 more negative the change score the greater the symptomatic improvement.

Outcome measures

Measure	Randomized Controlled Trial (RCT) Passive Treatment n=38 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of passive treatment in the randomized controlled trial.	Open Label Extension (OLE) Active Treatment n=38 Participants This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension during which participants received active (i.e., time-varying caloric vestibular simulation). Data is provided for change in scores after the 12 weeks of active treatment in the open label extension.
Change From Baseline in the Combined Measure of The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Parts I, II and III	-1.0 change in score on a scale from baseline Interval -5.0 to 6.3	-1.5 change in score on a scale from baseline Interval -8.8 to 10.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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. This measure will be evaluated as a safety outcome to assess whether device therapy negatively impacts balance or gait for participants with Parkinson's disease (day 197 score)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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).

A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

he 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

he 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Scores of ten seconds or less indicate normal mobility. Scores between 11 and 20 seconds are within normal limits for frail elderly and disabled patients.

Scores greater than 20 seconds suggest the person may need assistance outside and indicates further examination and intervention.

Scores of 30 seconds or more suggest the person may be prone to falls.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 months

Population: Full data collection was not completed as the study terminated prior to collection of outcome assessments for all participants.

a patient determined scale to assess how much their illness has improved or worsened relative to a baseline state at the beginning of the intervention.The Patient Global Impression of Improvement (PGI-I) is a tool used to measure a patient's perception of their condition following treatment. It is a single-item questionnaire that asks patients to rate their perceived change in condition on a scale from 1 (very much better) to 7 (very much worse).

Outcome measures

Outcome data not reported

Adverse Events

Experimental: Passive-active

Serious events: 7 serious events

Other events: 51 other events

Deaths: 1 deaths

Experimental: Active-active

Serious events: 6 serious events

Other events: 42 other events

Deaths: 1 deaths

Serious adverse events

Measure	Experimental: Passive-active n=69 participants at risk This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active (i.e., time-varying caloric vestibular stimulation) treatment. Treatment was \~20 minutes, 2x per day for 12 weeks, then a follow-up period without treatment for 16 weeks, then another 8 week treatment period with the active treatment.	Experimental: Active-active n=79 participants at risk This group received active (i.e. time-varying caloric vestibular stimulation) treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active treatment. Data obtained from this group was only utilized for exploratory outcome measures. Treatment was \~20 minutes, 2x per day for 12 weeks, then a follow-up period without treatment for 16 weeks, then another 8 week treatment period with the active treatment.
Cardiac disorders Atrial Fibrillation	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Respiratory, thoracic and mediastinal disorders Bilateral Pleural Effusions	0.00% 0/69 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Nervous system disorders Cerebral Vascular Accident	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Musculoskeletal and connective tissue disorders Right Knee Replacement surgery	0.00% 0/69 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple Myeloma	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Gastrointestinal disorders Pancreatitis	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin Cancer	0.00% 0/69 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Gastrointestinal disorders Partial Small Bowl Obstructive	0.00% 0/69 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Gastrointestinal disorders Acute Gastroenteritis with Dehydration	0.00% 0/69 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Infections and infestations ESCHERICHIA COLI URINARY TRACT INFECTION	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Injury, poisoning and procedural complications Fall	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	1.3% 1/79 • Number of events 2 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Infections and infestations Weakness secondary to urosepsis	1.4% 1/69 • Number of events 1 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	0.00% 0/79 • 8 months The clinicaltrials.gov definitions of AE and SAE were used

Other adverse events

Measure	Experimental: Passive-active n=69 participants at risk This group received passive treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active (i.e., time-varying caloric vestibular stimulation) treatment. Treatment was \~20 minutes, 2x per day for 12 weeks, then a follow-up period without treatment for 16 weeks, then another 8 week treatment period with the active treatment.	Experimental: Active-active n=79 participants at risk This group received active (i.e. time-varying caloric vestibular stimulation) treatment with the study device in a randomized controlled trial that immediately preceded this open label extension trial during which participants received active treatment. Data obtained from this group was only utilized for exploratory outcome measures. Treatment was \~20 minutes, 2x per day for 12 weeks, then a follow-up period without treatment for 16 weeks, then another 8 week treatment period with the active treatment.
Infections and infestations COVID-19	13.0% 9/69 • Number of events 9 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	15.2% 12/79 • Number of events 12 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Injury, poisoning and procedural complications Fall	23.2% 16/69 • Number of events 24 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	15.2% 12/79 • Number of events 25 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Nervous system disorders Dizziness	13.0% 9/69 • Number of events 11 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	6.3% 5/79 • Number of events 7 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Infections and infestations Nasopharyngitis	8.7% 6/69 • Number of events 7 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	8.9% 7/79 • Number of events 8 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
General disorders Medical device site discomfort	8.7% 6/69 • Number of events 6 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	2.5% 2/79 • Number of events 2 • 8 months The clinicaltrials.gov definitions of AE and SAE were used
Gastrointestinal disorders Nausea	7.2% 5/69 • Number of events 6 • 8 months The clinicaltrials.gov definitions of AE and SAE were used	5.1% 4/79 • Number of events 4 • 8 months The clinicaltrials.gov definitions of AE and SAE were used

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