An interventional study of Active, self-directed electrical stimulation of the median nerve in Tourette Syndrome and Tic Disorder, Chronic Motor or Vocal, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 15 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-10-05.
Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Treatment
A recent report (Morera Maiquez et al 2020) described reduced tic severity in people with Tourette syndrome during 1-minute epochs of median nerve stimulation (MNS) at 10 Hz. Among the various questions still to be answered is the question of whether a device to administer MNS is practical for use in a chronic, real-world setting. This study will recruit participants who complete the clinic-based, blinded, randomized controlled trial, https://clinicaltrials.gov/ct2/show/NCT04731714, to determine the real-world usage and apparent utility of median nerve stimulation in people with chronic tics.
Chronic tic disorders (CTD), including Tourette syndrome (TS), are associated with a substantially reduced quality of life (Evans et al 2016). Medication treatments are no more than 50-60% effective in randomized, controlled trials (RCTs), and are often discontinued due to unacceptable side effects (Thomas and Cavanna 2013). Behavioral therapies require ability to participate in therapy and a specially trained therapist (Scahill et al 2013), but weekly visits to psychologists are impractical for many Americans, especially in rural areas (Lin et al 2016). Patients strongly desire new treatment options (Cuenca et al 2015).
In June, 2020, Stephen Jackson's group at the University of Nottingham published a fascinating report in Current Biology on a potential novel treatment for tics (Morera Maiquez et al 2020). The radical new idea arose from observations associating movement inhibition with 8-14 Hz activity in motor cortex. They first showed that rhythmic 12 Hz peripheral stimulation of the median nerve evoked synchronous contralateral EEG activity over primary sensorimotor cortex, whereas arrhythmic stimulation at the same mean rate did not. As hypothesized, median nerve stimulation (MNS) at 12 Hz created small but statistically significant effects on initiation of voluntary movements. Importantly, they also demonstrated that this stimulation did not meaningfully impair concentration, suggesting that the effect did not operate through simple distraction. They went on to test 10 Hz MNS in 19 TS patients, and demonstrated using blinded video ratings a significant reduction in tic number and severity during 1-minute stimulation epochs vs 1-minute no-stimulation epochs. They noted that in some participants, benefit lasted beyond the end of the stimulation epoch [personal correspondence]. Videos accompanying the publication showed dramatic benefit during MNS in some subjects. Although the authors appropriately noted the steps needed to generalize these results to clinical practice, news reports already have led a number of TS patients to contact them asking for treatment. The Nottingham group has referred such inquiries from the U.S. to me as leader of our Wash.U. Tourette Association of America (TAA) Center of Excellence.
Among the various questions still to be answered is the question of whether such a device would be practical for use in the real world. This study will supply participants with a commercially available transcutaneous electrical nerve stimulation (TENS) units to use for median nerve stimulation as described in the Nottingham study. Participants will be told to use the device as much or as little as desired to see how such stimulation might be utilized in the real world.
Here the investigators propose (a) to determine the real-world usage and apparent utility of stimulation in people with chronic tics, and (b) to determine momentary self-rated efficacy and side effects of stimulation. The investigators will also compare results from this study to those from the "Peripheral induction of inhibitory brain circuits to treat Tourette's: pilot" study, from which participants will be drawn, in order to compare laboratory and real-world efficacy.
Aim 1. Determine the real-world usage and apparent utility of stimulation in people with chronic tics. Participants will be allowed to choose when and for how long to use the stimulation, thus simulating how patients would use the stimulation in their daily lives.
Aim 2. Determine momentary self-rated efficacy and side effects of stimulation, using surveys taken at the beginning and end of stimulation periods, as well as twice daily when prompted.
Aim 3. Compare results of this trial with those from "Peripheral induction of inhibitory brain circuits to treat Tourette's: pilot." Participants in this study will have been drawn from completers of the "peripheral induction" blinded RCT, allowing for clear comparisons between the laboratory conditions of the first study and the real-world conditions of the second.
Completion of these Aims will provide practical information that can inform a future, controlled clinical trial of chronic MNS delivered by a portable device.
240 studies on the registry are indexed under Tourette Syndrome; 40 are open to participants now.
This study's enrollment of 31 is below the median of 36 across 183 interventional studies indexed under Tourette Syndrome.
Browse Tourette Syndrome studies →Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.
Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Active, self-directed electrical stimulation of the right median nerve
Device: 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 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).
Also known as: Rhythmic MNS
Time Spent Using the Device Per Day of Use
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
Time frame: At study conclusion, up to 4 weeks
Time Spent Using the Device (Days Per Week)
Number of days per week the device was used
Time frame: At study conclusion, up to 4 weeks
Plan to Continue MNS (Median Nerve Stimulation)
Answered yes (from options yes / no / maybe) to the question, "Do you expect to continue to use the stimulator?"
Time frame: At study conclusion, up to 1 month
Change in Tic Frequency With Stimulation
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 .
Time frame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
Change in Tic Intensity With Stimulation
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.
Time frame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
Discomfort
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.
Time frame: 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.
CGI-I (Clinical Global Impression--Improvement)
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.
Time frame: At study conclusion, up to 4 weeks
CGI Efficacy Index: Side Effects
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.
Time frame: At study conclusion, up to 4 weeks
Mean Therapeutic Effect During Stimulator Use
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.
Time frame: At study conclusion, up to 4 weeks
Change in Self-reported Tic Severity
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.
Time frame: At beginning of study participation or up to 2 weeks prior, and again at end of study participation up to 4 weeks
Self-reported Duration of MNS Benefit, in Minutes
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.
Time frame: Monitored over the entire period of study participation, up to 4 weeks
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.
| Milestone | Active MNS |
|---|---|
| Started | 31 |
| Completed at least 1 ema (ecological momentary assessment) survey | 30 |
| Completed | 27 |
| Not completed | 4 |
| Withdrew: Lost to follow-up | 4 |
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
| minutes per day | Active MNS |
|---|---|
| Time Spent Using the Device Per Day of Use | 49.6 (24.2 to 117.2) |
Number of days per week the device was used
| days per week | Active MNS |
|---|---|
| Time Spent Using the Device (Days Per Week) | 1.5 (0.6 to 2.0) |
Answered yes (from options yes / no / maybe) to the question, "Do you expect to continue to use the stimulator?"
| Participants | Active MNS |
|---|---|
| Plan to Continue MNS (Median Nerve Stimulation) | 21 |
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 .
| score on a scale | Active MNS |
|---|---|
| All participants "turning ON" surveys | 3.1 ± 1.0 |
| All participants "turning OFF" surveys | 2.1 ± 1.1 |
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.
| score on a scale | Active MNS |
|---|---|
| All participants "turning ON" surveys | 2.9 ± 0.8 |
| All participants "turning OFF" surveys | 2.0 ± 1.1 |
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.
| units on a scale | Active MNS |
|---|---|
| Discomfort | 1.0 (0.6 to 1.5) |
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.
| units on a scale | Active MNS |
|---|---|
| CGI-I (Clinical Global Impression--Improvement) | 3.1 (2.7 to 3.4) |
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.
| units on a scale | Active MNS |
|---|---|
| CGI Efficacy Index: Side Effects | 1.2 ± 1.0 |
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.
| units on a scale | Active MNS |
|---|---|
| Mean Therapeutic Effect During Stimulator Use | 1.5 (1.1 to 1.9) |
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.
| units on a scale | Active MNS |
|---|---|
| baseline score | 35.4 ± 16.7 |
| final survey score | 34.6 ± 22.5 |
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.
| minutes | Active MNS |
|---|---|
| Self-reported Duration of MNS Benefit, in Minutes | 15 (10 to 45) |
Collected over through study completion, up to 4 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active MNS | 0/31 (0%) | 0/31 (0%) | 4/31 (12.9%) |
| Event | Active MNS |
|---|---|
| Skin IrritationSkin and subcutaneous tissue disorders | 2/31 |
| Stimulation Limited Muscle DexterityNervous system disorders | 2/31 |
Everyone who signed an informed consent document for this study.
| Age, Continuous(years) | Active MNS |
|---|---|
| Mean | 34.5 ± 16.6 |
| Sex: Female, Male(Participants) | Active MNS |
|---|---|
| Female | 11 |
| Male | 20 |
| Ethnicity (NIH/OMB)(Participants) | Active MNS |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 30 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Active MNS |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 28 |
| More than one race | 1 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Active MNS |
|---|---|
| United States | 31 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — All IPD other than PHI (protected health information) will be shared on OSF.io or as a supplement to publication of results.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Available within 6 months after publication of key results
Access criteria: Individual participant data (IPD) will be freely available under a CC0 license (Creative Commons public domain dedication, https://creativecommons.org/publicdomain/zero/1.0/).
Data sharing details ↗ · osf.io
Ran from Nov 2021 to primary completion in Apr 2022, 5 months.
Results were first posted in Oct 2023, 1 year 5 months after primary completion.
Of 65 non-industry interventional studies with no phase under Tourette Syndrome, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 50. This study's 5 months is below that.
Counting every sponsor, half of 65 studies reached it within 33 months; a quarter within 22 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.
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