Trial Outcomes & Findings for Open-label MNS for Tourette Syndrome (NCT NCT05016765)

NCT ID: NCT05016765

Last Updated: 2023-10-05

Results Overview

Number of minutes per day the device was used, only counting days in which the device was turned on, over the four-week period after the initial visit

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 31 participants
• Primary outcome timeframe: At study conclusion, up to 4 weeks
• Results posted on: 2023-10-05

Participant Flow

Participants were recruited from those 32 participants who completed an in person RCT (randomized controlled trial; registration number NCT04731714). One RCT participant did not choose to participate in this open-label extension. Recruitment occurred between November 2021 and April 2022.

Participant milestones

Measure	Active MNS Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Overall Study STARTED	31
Overall Study Completed At Least 1 EMA (Ecological Momentary Assessment) Survey	30
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure

Active MNS Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Overall Study Lost to Follow-up

4

Baseline Characteristics

Open-label MNS for Tourette Syndrome

Baseline characteristics by cohort

Measure	Active MNS n=31 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Age, Continuous	34.5 years STANDARD_DEVIATION 16.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants

PRIMARY outcome

Timeframe: At study conclusion, up to 4 weeks

Number of minutes per day the device was used, only counting days in which the device was turned on, over the four-week period after the initial visit

Outcome measures

Measure

Active MNS n=31 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Time Spent Using the Device Per Day of Use

49.6 minutes per day Interval 24.2 to 117.2

PRIMARY outcome

Timeframe: At study conclusion, up to 4 weeks

Population: All participants enrolled in study

Number of days per week the device was used

Outcome measures

Measure

Active MNS n=31 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Time Spent Using the Device (Days Per Week)

1.5 days per week Interval 0.6 to 2.0

PRIMARY outcome

Timeframe: At study conclusion, up to 1 month

Population: All participants who completed the final survey

Answered yes (from options yes / no / maybe) to the question, "Do you expect to continue to use the stimulator?"

Outcome measures

Measure

Active MNS n=27 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Plan to Continue MNS (Median Nerve Stimulation)

21 Participants

PRIMARY outcome

Timeframe: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks

Population: All participants with at least one on-off survey pair during the study period

Change in self-reported tic frequency on the frequency item (score range from 0 = no tics [better] to 5 = always [worse]) from the Yale Global Tic Severity Scale (YGTSS) from the beginning to the end of each stimulation period. Participants were instructed to answer this question every time they turned on the device and every time they turned it off, every day for 4 weeks. The difference between the turning off score and the previous turning on score was averaged across all ratings completed during the 4 weeks of the trial. The wording of the score anchors is provided at https://osf.io/7pjk4 .

Outcome measures

Measure	Active MNS n=25 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Change in Tic Frequency With Stimulation All participants "turning ON" surveys	3.1 score on a scale Standard Deviation 1.0
Change in Tic Frequency With Stimulation All participants "turning OFF" surveys	2.1 score on a scale Standard Deviation 1.1

PRIMARY outcome

Timeframe: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks

Population: All participants with at least one on-off survey pair during the study period.

Change in self-reported tic intensity on the intensity item (score range from 0 = no tics [better] to 5 = severe intensity [worse]) from the Yale Global Tic Severity Scale (YGTSS) from the beginning to the end of each stimulation period. Participants were instructed to answer this question every time they turned on the device and every time they turned it off, every day for 4 weeks. The difference between the turning off score and the previous turning on score was averaged across all ratings completed during the 4 weeks of the trial.

Outcome measures

Measure	Active MNS n=25 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Change in Tic Intensity With Stimulation All participants "turning ON" surveys	2.9 score on a scale Standard Deviation 0.8
Change in Tic Intensity With Stimulation All participants "turning OFF" surveys	2.0 score on a scale Standard Deviation 1.1

PRIMARY outcome

Timeframe: Recorded every time the device was turned off, and every time the participant was prompted by a text to fill out the survey if the device was on when the text was received, up to 4 weeks.

Population: All participants who completed the discomfort question at least once during the study after initial training.

Mean discomfort while using the stimulator, on a 0-3 scale adapted from the Clinical Global Impression - Improvement [CGI-I] Efficacy Index. Specifically, the prompt was "How much DISCOMFORT did the stimulation cause?", and the participant selected one of the following responses:

0 = NO discomfort

1. = discomfort noticeable, but not severe enough to concern me or to turn it off

2. = enough discomfort, impairment of functioning or social embarrassment that I would only keep it on if the benefit was considerable

3. = caused discomfort, impairment of functioning or social embarrassment to a degree that any treatment benefit was not worth leaving it on Higher values represent a worse outcome. Discomfort was reported at the end of each stimulation period, and at random times twice daily between 9a.m. and 9p.m. when prompted by text message, if the device was on when the text was received.

Outcome measures

Measure

Active MNS n=26 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Discomfort

1.0 units on a scale Interval 0.6 to 1.5

SECONDARY outcome

Timeframe: At study conclusion, up to 4 weeks

Population: All participants who completed the final survey.

Overall impact of the stimulation on symptoms throughout the study period:

1. = Very much improved - nearly all better; good level of functioning; minimal symptoms; represents a very substantial change

2. = Much improved - notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain

3. = Minimally improved - slightly better with little or no clinically meaningful reduction of symptoms. Represents very little change in basic clinical status, level of care, or functional capacity

4. = No change - symptoms remain essentially unchanged

5. = Minimally worse - slightly worse but may not be clinically meaningful; may represent very little change in basic clinical status, level of care, or functional capacity

6. = Much worse - clinically significant increase in symptoms and diminished functioning

7. = Very much worse - severe exacerbation of symptoms and loss of functioning On this scale, lower numbers indicate a better outcome.

Outcome measures

Measure

Active MNS n=27 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

CGI-I (Clinical Global Impression--Improvement)

3.1 units on a scale Interval 2.7 to 3.4

SECONDARY outcome

Timeframe: At study conclusion, up to 4 weeks

Population: All participants who completed the final survey.

Overall discomfort from stimulation throughout the study period. The prompt for this survey question was: "On average, over the course of the study, how much DISCOMFORT did the stimulation cause? (If discomfort is the wrong word, please substitute any negative effects or side effects of stimulation.)" Participants chose one of the following answers:

0 no discomfort

1. discomfort noticeable, but not severe enough to concern me or to turn it off

2. enough discomfort, impairment of functioning or social embarrassment that I would only keep it on if the benefit was considerable

3. caused discomfort, impairment of functioning or social embarrassment to a degree that any treatment benefit was not worth leaving it on On this scale, lower numbers represent a better outcome.

Outcome measures

Measure

Active MNS n=27 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

CGI Efficacy Index: Side Effects

1.2 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: At study conclusion, up to 4 weeks

Population: All participants who completed the final survey.

Mean self-rated therapeutic effect (from the modified CGI Efficacy Index) when device is on, reported at the end of the study. Specifically, the prompt for this question was "On average, over the course of the study, how much did your tics IMPROVE during stimulation?" Participants chose one of the following answers:

0 Unchanged or worse

1. Minimal - Slight improvement that doesn't decrease the overall impact of symptoms.

2. Moderate - Decided improvement. Partial remission of symptoms

3. Marked - Vast improvement. Complete or nearly complete remission of all symptoms On this scale, higher numbers represent a better outcome.

Outcome measures

Measure

Active MNS n=27 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Mean Therapeutic Effect During Stimulator Use

1.5 units on a scale Interval 1.1 to 1.9

SECONDARY outcome

Timeframe: At beginning of study participation or up to 2 weeks prior, and again at end of study participation up to 4 weeks

Population: All participants with ATQ scores both at baseline and during final survey (those who completed final survey more than 4 weeks after completing the study were excluded).

Self-rated tic severity over the past week using the Adult Tic Questionnaire (ATQ), first rating at (or within 2 weeks prior to) the beginning of study participation and second rating at the end of study participation. Higher ATQ scores reflect a worse outcome. For each tic present in the past week, its severity score is the sum of its frequency score (0-4, 4 worst, occurring "almost all the time during the day") and its intensity score (0-4, 4 worst). The ATQ severity score is the sum of the severity score for each of up to 27 tics present in the past week. The minimum possible severity score on the ATQ is 0, indicating that no tics were present in the past week. The maximum possible severity score on the ATQ indicates is 216, indicating that a tic of each of the 27 types listed was present in the past week, each with an item severity score of 8 = 4 + 4.

Outcome measures

Measure	Active MNS n=25 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Change in Self-reported Tic Severity baseline score	35.4 units on a scale Standard Deviation 16.7
Change in Self-reported Tic Severity final survey score	34.6 units on a scale Standard Deviation 22.5

SECONDARY outcome

Timeframe: Monitored over the entire period of study participation, up to 4 weeks

Population: All participants who answered this question on the final survey

On the survey at the end of study participation, the relevant question asked: "On average, over the course of the study, how long do you think the improvement in your tics lasted after you turned off the device? Give answer in minutes. Enter 0 (zero) if improvement with stimulation stopped immediately when you turned the device off." On this item, higher answers indicate a better outcome.

Outcome measures

Measure

Active MNS n=21 Participants Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).

Self-reported Duration of MNS Benefit, in Minutes

15 minutes Interval 10.0 to 45.0

Adverse Events

Active MNS

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Active MNS n=31 participants at risk Active, self-directed electrical stimulation of the median nerve: Electrical stimulation of the median nerve (12 Hz, pulse width 200µs), initially at the threshold needed to see movement of the right thumb with right median nerve stimulation. After initial training with the device and education in the rationale for suprathreshold stimulation, participants will choose timing and intensity of stimulation based on their momentary symptom severity and their experience with the treatment since the beginning of the study. Participant can choose right or left median nerve (we will suggest their nondominant hand to minimize interference with daily activities).
Skin and subcutaneous tissue disorders Skin Irritation	6.5% 2/31 • through study completion, up to 4 weeks Data were collected by open-ended question on the final survey regarding the full period of time up to four weeks from enrollment through completing the final survey.
Nervous system disorders Stimulation Limited Muscle Dexterity	6.5% 2/31 • through study completion, up to 4 weeks Data were collected by open-ended question on the final survey regarding the full period of time up to four weeks from enrollment through completing the final survey.

Additional Information

Kevin J. Black, M.D.

Washington University School of Medicine

Phone: 1-314-362-5041

Email: kevin@wustl.edu

Results disclosure agreements

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