Tourette SyndromeMNSNCT04731714

Median Nerve Stimulation Pilot

A study testing Rhythmic median nerve stimulation and Arrhythmic median nerve stimulation in people with Tourette Syndrome and Tic Disorders, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 15 to 64 years
Conditions the study is for: Tourette Syndrome, Tic Disorders, Tic Disorder, Chronic Motor or Vocal
What is being tested?: Rhythmic median nerve stimulation and Arrhythmic median nerve stimulation
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 1 siteUnited States
Study dates: 15 Jul 2021to 27 Apr 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 15 to 64 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Age 15-64 inclusive at initial screening visit
Informed consent by adult subject; assent by child and informed consent by guardian
Current Tourette's Disorder or Persistent (Chronic) Tic Disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5
At least 1 tic per minute (average) during the first 5-min. baseline video session on the first visit (as scored during the session by the investigator)

Who cannot join

Unable to complete study procedures for any reason
Has an implanted device that could be affected by electrical current
Pregnancy known to participant or (for children) to the parent
Known or suspected primary genetic syndrome (e.g. Down syndrome, Fragile X)
Intellectual disability (known, or likely from history and examination)
Head trauma with loss of consciousness for more than 5 minutes

Show all 12Show fewer

Significant neurologic disease, not counting TS (exceptions include febrile seizures or uncomplicated migraine)
Severe or unstable systemic illness
Factors (such as exaggerated signs) that in the judgment of the principal investigator make the video recording or YGTSS an inaccurate assessment of tic severity
Judged by investigator to be unlikely to complete study procedures or to return for later visits
Change in somatic or psychotherapeutic treatment in the 2 weeks preceding the first stimulation visit
Planned change in somatic or psychotherapeutic treatment between the 2 stimulation visits

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University School of Medicine, Movement Disorders Center
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Peripheral Induction of Inhibitory Brain Circuits to Treat Tourette's: Pilot

Results from the University of Nottingham suggested that rhythmic median nerve stimulation (MNS) improves tic symptoms in Tourette syndrome (TS). The investigators will (1) provide a first replication of their study, (2) test the hypothesized electrophysiological mechanism and rule out a placebo effect as cause for the symptomatic benefit, and (3) gather information on the duration of effect after the end of stimulation and on individual characteristics that predict improvement with simulation. Completion of these Aims will give a clear go/no-go signal for a future clinical trial of chronic MNS delivered by a yet-to-be-developed wristwatch-style device.

NOTE: This study is not intended to evaluate a specific device for future use. Rather it is a study to determine the action of pulsed electrical stimulation on tic symptoms and to gain early evidence of effectiveness. This is a non-significant risk device study.

Read the detailed description

Chronic tic disorders (CTD), including Tourette syndrome (TS), are associated with a substantially reduced quality of life. Medication treatments are no more than 50-60% effective in randomized controlled trials, and are often discontinued due to unacceptable side effects. Behavioral therapies require ability to participate in therapy and a specially trained therapist, but weekly visits to psychologists are impractical for many Americans, especially in rural areas. Patients strongly desire new treatment options.

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. 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. 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.

The hypotheses of this project are that the tic benefits reported by the Nottingham investigators are replicable, that they are specific to rhythmic stimulation, which alone entrained cortical activity, rather than to a placebo effect, and that they endure past the end of stimulation.

This project (a) will replicate the Nottingham findings using identical methods, and (b) will test rhythmic MNS against a placebo treatment (arrhythmic MNS at the same mean frequency). It also will gather additional preliminary data needed for a future R01 application, including response and tolerability with longer (5-minute) stimulation blocks, and the duration of benefit after the end of a stimulation block.

Conditions: Tourette Syndrome, Tic Disorders, Tic Disorder, Chronic Motor or Vocal
Being tested: Rhythmic median nerve stimulation, Arrhythmic median nerve stimulation
Keywords: Tourette, Tic, Transcutaneous Electric Nerve Stimulation, Median Nerve
Medical subject headings: Tourette Syndrome, Tic Disorders, Tics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Rhythmic median nerve stimulationDevice
Also called Rhythmic MNS
Square-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected ~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.
Arrhythmic median nerve stimulationDevice
Also called Arrhythmic MNS
Square-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected ~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.

Study groups in NCT04731714
Study group	Role	What they receive
Experimental: rhythmic MNS, then arrhythmic MNS	Other	Participants will complete two stimulation sessions, at least a week apart. The first session involves rhythmic MNS and the second uses arrhythmic MNS. Receives: Device: Rhythmic median nerve stimulation; Device: Arrhythmic median nerve stimulation
Experimental: arrhythmic MNS, then rhythmic MNS	Other	Participants will complete two stimulation sessions, at least a week apart. The first session involves arrhythmic MNS and the second uses rhythmic MNS. Receives: Device: Rhythmic median nerve stimulation; Device: Arrhythmic median nerve stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Tic Frequency From When MNS is Turned Off
The number of tics per minute is assessed by an expert rater blind to condition and time point. Mean tic frequency was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation, who reported tics in the last 40 seconds of the block to minimize carryover effects. A Mixed Models Analysis was used to test statistical significance; it included a factor for possible within-day carryover effect and used a logarithmic transformation for tic count. Data reported here have been back-transformed to the number of tics in the last 40 s of the stimulation blocks.
Measured: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)
Change in Tic Severity From When MNS is Turned Off
Severity is rated on a 5-point scale for each occurrence of any tic. The scale is the Intensity item from the Yale Global Tic Severity Scale [YGTSS], which uses integer scores from 0 (no tics) to 5 (severe intensity). Mean tic severity was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation.
Measured: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)
Change in Tic Frequency During Rhythmic MNS (vs. Arrhythmic MNS)
The number of tics per minute is assessed by an expert rater blind to condition and time point. Change in tic frequency from baseline (stimulation off) is compared between 5-minute MNS-on epochs on the rhythmic vs. the arrhythmic day. Subjects who do not complete both stimulation visits will not be included in this analysis. The hypothesized change is greater improvement (off to on) with rhythmic vs. arrhythmic stimulation. This analysis includes the first six 5-minute blocks on each MNS day (i.e., the blocks that all participants complete). MNS was administered throughout blocks 6 and 8 only. Tic frequency in block 0 (baseline, before any stimulation) on the same day was a covariate in the statistical model.
Measured: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9
Change in Tic Severity During Rhythmic MNS (vs. Arrhythmic MNS)
Overall tic severity for each 5-minute block is rated once on a 5-point scale by an expert blind to condition and time point. The scale is the Intensity item from the Yale Global Tic Severity Scale [YGTSS], which uses integer scores from 0 (no tics) to 5 (severe intensity). Change in tic severity from baseline (stimulation off) is compared between 5-minute MNS-on epochs on the rhythmic vs. the arrhythmic day. Subjects who do not complete both stimulation visits will not be included in this analysis. The hypothesized change was greater improvement (off to on) with rhythmic vs. arrhythmic stimulation. This analysis includes the first six 5-minute blocks on each MNS day (i.e., the blocks that all participants complete). MNS was administered throughout blocks 6 and 8 only. Tic frequency in block 0 (baseline, before any stimulation) on the same day was a covariate in the statistical model.
Measured: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9

Secondary outcomes (7)

Change in Tic Severity After MNS Ends
We compared the change in tic frequency from baseline, during each 1-minute-long period following the end of stimulation. Here baseline means the tic frequency during the last 5 minutes of MNS from the same day (block 8). Last observation carried forward was used for participants who had less than 20 minutes of data following block 8.
Measured: up to 20 minutes after the end of stimulation at each study visit up to 1 month
CGI-I, Participant
Clinical Global Impression of Improvement (CGI-I), rated by participant. The CGI-I is a 7-point scale ranging from 1 = very much improved to 7 = very much worse.
Measured: 5-25 minutes after the end of stimulation at each study visit up to 1 month
CGI-I, Investigator
Clinical Global Impression of Improvement (CGI-I), rated by investigator. The CGI-I is a 7-point scale ranging from 1 = very much improved to 7 = very much worse.
Measured: 5-25 minutes after the end of stimulation at each study visit up to 1 month
Rating of Therapeutic Effect Using the CGI Efficacy Index
Participant rates peak improvement experienced during the visit using the 4-point scale of the CGI (Unchanged or worse; Minimal - Slight improvement that doesn't decrease the overall impact of symptoms*; Moderate - Decided improvement. Partial remission of symptoms; Marked - Vast improvement. Complete or nearly complete remission of all symptoms). * = "Minimal" option anchor text slightly edited from original. The number provided is the number of participants who rated each visit as moderate or marked.
Measured: 5-25 minutes after the end of stimulation at each study visit up to 1 month
VAS (Visual Analog Scale) Rating of Premonitory Urge Severity
Participant rates the maximal severity of any premonitory urges over the preceding minute, from 0=no premonitory urge to 100=maximally uncomfortable premonitory urge, using a Visual Analog Scale.
Measured: At the end of each 5-min. MNS on or off block through block 9, at each study visit
Rating of Discomfort Using the CGI Efficacy Index (Edited)
Participant rates peak discomfort experienced during the visit using the 4-point scale of the CGI: "Overall, today, how much DISCOMFORT did the stimulation cause? If discomfort is the wrong word, please substitute any negative effects or side effects of stimulation. (No discomfort; Discomfort noticeable, but not severe enough to concern me or to turn it off; Enough discomfort, impairment of functioning or social embarrassment that I would only keep it on if the benefit was considerable; Caused discomfort, impairment of functioning or social embarrassment to a degree that any treatment benefit was not worth leaving it on). The number provided is the number of visits where discomfort is rated as none or minimal.
Measured: 5-25 minutes after the end of stimulation at each study visit up to 1 month
Blindedness Assessment
Participants guess at each study visit whether they received the active or sham MNS condition, and rate their certainty for that guess on a 0-3 scale (0 = pure guess, 3 = certain). The number reported here is the number of visits for which the participant guessed correctly (active vs. sham MNS).
Measured: 5-25 minutes after the end of stimulation at each study visit up to 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Jul 202127 Apr 2022

First posted1 Feb 2021
Study start15 Jul 2021
Primary completion27 Apr 2022
Study completion27 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Tourette SyndromeStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: After screening and characterizing symptoms and other demographic and clinical features, all participants will complete two stimulation sessions, at least a week apart. These are identical except that one session uses rhythmic and one uses arrhythmic MNS with the same number of total pulses per minute. Session order is randomized and participants are blinded to order. Biological carryover effects are very unlikely. Tics before, during and after stimulation epochs are video recorded for later analysis blind to time, stimulation (on vs. off), and stimulation type (rhythmic vs. arrhythmic). NOTE: This study is not intended to evaluate a specific device for future use. Rather it is a study to determine the action of pulsed electrical stimulation on tic symptoms and to gain early evidence of effectiveness. This is a non-significant risk device study.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04731714
Sponsor's protocol ID: 202011092
Other IDs: UL1TR002345
Acronym: MNS
Status last verified: Sep 2023
First submitted: 13 Jan 2021
Last updated: 5 Oct 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Yes: Video recordings will not be shared, as they cannot feasibly be de-identified. All other individual participant data (excluding PHI) will be collected and stored on REDCap (redcap.wustl.edu) and will be shared on the Open Science Framework (OSF, at https://osf.io/mtbzf/).

Publications

Morera Maiquez B, Sigurdsson HP, Dyke K, Clarke E, McGrath P, Pasche M, Rajendran A, Jackson GM, Jackson SR. Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome. Curr Biol. 2020 Jun 22;30(12):2334-2342.e3. doi: 10.1016/j.cub.2020.04.044. Epub 2020 Jun 4.
PubMed 32502412
Iverson AM, Arbuckle AL, Ueda K, Song DY, Bihun EC, Koller JM, Wallendorf M, Black KJ. Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial. J Clin Med. 2023 Mar 27;12(7):2514. doi: 10.3390/jcm12072514.
PubMed 37048598
Iverson AM, Arbuckle AL, Ueda K, Song DY, Bihun EC, Koller JM, Wallendorf M, Black KJ. Peripheral nerve induction of inhibitory brain circuits to treat Tourette syndrome: A randomized crossover trial. medRxiv [Preprint]. 2023 Feb 6:2023.02.01.23285304. doi: 10.1101/2023.02.01.23285304.
PubMed 36778375

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Deep Brain Stimulation Therapy in Movement Disorders
Parkinson's Disease
Recruiting
Exploring the Role of Neuroactive Steroids in Tourette Syndrome
Tourette Syndrome in Children
Active, not recruiting
Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression
Tourette Syndrome
Recruiting
Integrating Exposure and Response Prevention and Habit Reversal Techniques to Treat a Tourettic Subtype of Obsessive-Compulsive Disorder (Tourettic OCD)
Obsessive - Compulsive Disorder, Tic Disorder, Chronic Motor or Vocal
RecruitingPhase 2
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
Neurodevelopmental Disorders, Autism

All Tourette Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Peripheral Induction of Inhibitory Brain Circuits to Treat Tourette's: Pilot
ClinicalTrials.gov ID: NCT04731714
Acronym / sponsor ID: MNS / 202011092
Conditions: Tourette Syndrome, Tic Disorders, Tic Disorder, Chronic Motor or Vocal
Keywords: Tourette, Tic, Transcutaneous Electric Nerve Stimulation, Median Nerve
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Collaborators: National Center for Advancing Translational Sciences (NCATS)
Study start: 15 Jul 2021 (actual)
Primary completion: 27 Apr 2022 (actual)
Study completion: 27 Apr 2022 (actual)
First posted: 1 Feb 2021 (actual)
Results: Posted 5 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2
Model description: After screening and characterizing symptoms and other demographic and clinical features, all participants will complete two stimulation sessions, at least a week apart. These are identical except that one session uses rhythmic and one uses arrhythmic MNS with the same number of total pulses per minute. Session order is randomized and participants are blinded to order. Biological carryover effects are very unlikely. Tics before, during and after stimulation epochs are video recorded for later analysis blind to time, stimulation (on vs. off), and stimulation type (rhythmic vs. arrhythmic). NOTE: This study is not intended to evaluate a specific device for future use. Rather it is a study to determine the action of pulsed electrical stimulation on tic symptoms and to gain early evidence of effectiveness. This is a non-significant risk device study.

Arm	Type	Receives
Experimental: rhythmic MNS, then arrhythmic MNS	Other	Device: Rhythmic median nerve stimulation, Device: Arrhythmic median nerve stimulationParticipants will complete two stimulation sessions, at least a week apart. The first session involves rhythmic MNS and the second uses arrhythmic MNS.
Experimental: arrhythmic MNS, then rhythmic MNS	Other	Device: Rhythmic median nerve stimulation, Device: Arrhythmic median nerve stimulationParticipants will complete two stimulation sessions, at least a week apart. The first session involves arrhythmic MNS and the second uses rhythmic MNS.

Who may qualify

Ages: 15 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Age 15-64 inclusive at initial screening visit
Informed consent by adult subject; assent by child and informed consent by guardian
Current Tourette's Disorder or Persistent (Chronic) Tic Disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5
At least 1 tic per minute (average) during the first 5-min. baseline video session on the first visit (as scored during the session by the investigator)

Key exclusion criteria (12 listed)

Unable to complete study procedures for any reason
Has an implanted device that could be affected by electrical current
Pregnancy known to participant or (for children) to the parent
Known or suspected primary genetic syndrome (e.g. Down syndrome, Fragile X)
Intellectual disability (known, or likely from history and examination)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Rhythmic median nerve stimulationAlso: Rhythmic MNSSquare-wave 200 µs pulses triggered by computer at 12 Hz, at the threshold for thumb movement (expected ~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.	Device	Experimental: arrhythmic MNS, then rhythmic MNS, Experimental: rhythmic MNS, then arrhythmic MNS
Arrhythmic median nerve stimulationAlso: Arrhythmic MNSSquare-wave 200 µs pulses triggered by computer at random intervals with a mean rate of 12 Hz (as described in Morera Maiquez et al., 2020), at the threshold for thumb movement (expected ~2-15mA), applied to surface electrodes over the median nerve at the right wrist (conductive gel, 30 mm apart center-to-center, anode distal). This is a non-significant risk device study.	Device	Experimental: arrhythmic MNS, then rhythmic MNS, Experimental: rhythmic MNS, then arrhythmic MNS

Primary outcome

Change in Tic Frequency From When MNS is Turned Off
Time frame: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)
The number of tics per minute is assessed by an expert rater blind to condition and time point. Mean tic frequency was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation, who reported tics in the last 40 seconds of the block to minimize carryover effects. A Mixed Models Analysis was used to test statistical significance; it included a factor for possible within-day carryover effect and used a logarithmic transformation for tic count. Data reported here have been back-transformed to the number of tics in the last 40 s of the stimulation blocks.
Change in Tic Severity From When MNS is Turned Off
Time frame: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)
Severity is rated on a 5-point scale for each occurrence of any tic. The scale is the Intensity item from the Yale Global Tic Severity Scale [YGTSS], which uses integer scores from 0 (no tics) to 5 (severe intensity). Mean tic severity was compared in on vs. off 1-minute stimulation epochs on the rhythmic MNS day. This analysis replicates that of Study 3 in the Morera Maiquez et al 2020 citation.
Change in Tic Frequency During Rhythmic MNS (vs. Arrhythmic MNS)
Time frame: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9
The number of tics per minute is assessed by an expert rater blind to condition and time point. Change in tic frequency from baseline (stimulation off) is compared between 5-minute MNS-on epochs on the rhythmic vs. the arrhythmic day. Subjects who do not complete both stimulation visits will not be included in this analysis. The hypothesized change is greater improvement (off to on) with rhythmic vs. arrhythmic stimulation. This analysis includes the first six 5-minute blocks on each MNS day (i.e., the blocks that all participants complete). MNS was administered throughout blocks 6 and 8 only. Tic frequency in block 0 (baseline, before any stimulation) on the same day was a covariate in the statistical model.
Change in Tic Severity During Rhythmic MNS (vs. Arrhythmic MNS)
Time frame: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9
Overall tic severity for each 5-minute block is rated once on a 5-point scale by an expert blind to condition and time point. The scale is the Intensity item from the Yale Global Tic Severity Scale [YGTSS], which uses integer scores from 0 (no tics) to 5 (severe intensity). Change in tic severity from baseline (stimulation off) is compared between 5-minute MNS-on epochs on the rhythmic vs. the arrhythmic day. Subjects who do not complete both stimulation visits will not be included in this analysis. The hypothesized change was greater improvement (off to on) with rhythmic vs. arrhythmic stimulation. This analysis includes the first six 5-minute blocks on each MNS day (i.e., the blocks that all participants complete). MNS was administered throughout blocks 6 and 8 only. Tic frequency in block 0 (baseline, before any stimulation) on the same day was a covariate in the statistical model.

7 secondary outcomes

Change in Tic Severity After MNS Ends
Time frame: up to 20 minutes after the end of stimulation at each study visit up to 1 month
CGI-I, Participant
Time frame: 5-25 minutes after the end of stimulation at each study visit up to 1 month
CGI-I, Investigator
Time frame: 5-25 minutes after the end of stimulation at each study visit up to 1 month
Rating of Therapeutic Effect Using the CGI Efficacy Index
Time frame: 5-25 minutes after the end of stimulation at each study visit up to 1 month
VAS (Visual Analog Scale) Rating of Premonitory Urge Severity
Time frame: At the end of each 5-min. MNS on or off block through block 9, at each study visit
Rating of Discomfort Using the CGI Efficacy Index (Edited)
Time frame: 5-25 minutes after the end of stimulation at each study visit up to 1 month
Blindedness Assessment
Time frame: 5-25 minutes after the end of stimulation at each study visit up to 1 month

Results and safety

Results posted to the registry on 5 Oct 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental: Rhythmic MNS, Then Arrhythmic MNS	16	16
Experimental: Arrhythmic MNS, Then Rhythmic MNS	16	16

Primary outcome: Change in Tic Frequency From When MNS is Turned Off

Time frame: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks). Least squares mean (95% Confidence Interval). Unit: Tic frequency (number of tics in 40 s)

Measure	All Participants n = 32
Stimulation Off	12.1 (9.3 to 15.8)
Stimulation On	8.9 (6.6 to 11.8)

All Participants: p = 0.0104, Mixed Models Analysis

Population analysed: All participants in the study, 4 blocks for each participant (2 on, 2 off, in random order)

Primary outcome: Change in Tic Severity From When MNS is Turned Off

Time frame: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks). Least squares mean (95% Confidence Interval). Unit: units on a scale

Measure	All Participants n = 32
Stimulation Off	2.5 (2.2 to 2.7)
Stimulation On	2.3 (2.0 to 2.6)

All Participants: p = 0.079, Mixed Models Analysis

Population analysed: All participants in the study, 4 blocks for each participant (2 on, 2 off, in random order)

Primary outcome: Change in Tic Frequency During Rhythmic MNS (vs. Arrhythmic MNS)

Time frame: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9. Least squares mean (95% Confidence Interval). Unit: Tic frequency (number of tics in 5 min.)

Measure	All Participants n = 32
Arrhythmic Block 5	85.8 (69.2 to 102.4)
Arrhythmic Block 6	63.3 (46.5 to 80.2)
Arrhythmic Block 7	74.2 (57.3 to 91.2)
Arrhythmic Block 8	57.7 (40.8 to 74.5)
Arrhythmic Block 9	65.0 (48.4 to 81.6)
Rhythmic Block 5	85.9 (69.7 to 102.1)
Rhythmic Block 6	61.8 (45.4 to 78.2)
Rhythmic Block 7	67.5 (51.0 to 83.9)

All Participants: p = 0.9222, Mixed Models Analysis

Population analysed: All participants in the study

Primary outcome: Change in Tic Severity During Rhythmic MNS (vs. Arrhythmic MNS)

Time frame: During 5-minute MNS stimulation on or off blocks 0, 5, 6, 7, 8 and 9. Least squares mean (95% Confidence Interval). Unit: units on a scale

Measure	All Participants n = 32
Arrhythmic Block 5	3.4 (3.1 to 3.6)
Arrhythmic Block 6	3.2 (2.9 to 3.5)
Arrhythmic Block 7	3.4 (3.1 to 3.6)
Arrhythmic Block 8	3.0 (2.7 to 3.3)
Arrhythmic Block 9	3.1 (2.8 to 3.3)
Rhythmic Block 5	3.3 (3.0 to 3.6)
Rhythmic Block 6	3.2 (2.9 to 3.4)
Rhythmic Block 7	3.2 (2.9 to 3.5)

All Participants: p = 0.7995, Mixed Models Analysis

Population analysed: All participants in the study

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From enrollment through final study visit, up to 1 month. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Experimental: Rhythmic MNS	0 of 32 (0%)	4 of 32 (12.5%)	0 of 32
Experimental: Arrhythmic MNS	0 of 32 (0%)	3 of 32 (9.4%)	0 of 32

Limitations and caveats (from the sponsor): We did not test other variations on MNS, so we cannot address the specificity of the median nerve (vs. any other peripheral nerve), the specificity of 10-12 Hz as the stimulation frequency, or whether there is a lateral preference for MNS benefit.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 32502412Morera Maiquez B, Sigurdsson HP, Dyke K, Clarke E, McGrath P, Pasche M, Rajendran A, Jackson GM, Jackson SR. Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome. Curr Biol. 2020 Jun 22;30(12):2334-2342.e3. doi: 10.1016/j.cub.2020.04.044. Epub 2020 Jun 4.
Derived from this study: PubMed 37048598Iverson AM, Arbuckle AL, Ueda K, Song DY, Bihun EC, Koller JM, Wallendorf M, Black KJ. Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial. J Clin Med. 2023 Mar 27;12(7):2514. doi: 10.3390/jcm12072514.
Derived from this study: PubMed 36778375Iverson AM, Arbuckle AL, Ueda K, Song DY, Bihun EC, Koller JM, Wallendorf M, Black KJ. Peripheral nerve induction of inhibitory brain circuits to treat Tourette syndrome: A randomized crossover trial. medRxiv [Preprint]. 2023 Feb 6:2023.02.01.23285304. doi: 10.1101/2023.02.01.23285304.
Study protocol (follow link under "Protocol")Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Video recordings will not be shared, as they cannot feasibly be de-identified. All other individual participant data (excluding PHI) will be collected and stored on REDCap (redcap.wustl.edu) and will be shared on the Open Science Framework (OSF, at https://osf.io/mtbzf/).

Related trials for Tourette Syndrome

Recruiting
Deep Brain Stimulation Therapy in Movement Disorders
Parkinson's Disease
Recruiting
Exploring the Role of Neuroactive Steroids in Tourette Syndrome
Tourette Syndrome in Children
Active, not recruiting
Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression
Tourette Syndrome
Recruiting
Integrating Exposure and Response Prevention and Habit Reversal Techniques to Treat a Tourettic Subtype of Obsessive-Compulsive Disorder (Tourettic OCD)
Obsessive - Compulsive Disorder, Tic Disorder, Chronic Motor or Vocal
RecruitingPhase 2
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
Neurodevelopmental Disorders, Autism

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kevin J Black, MD principal investigator

Washington University Medical School

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Tic Frequency From When MNS is Turned Off (time frame: During the 1-minute on and 1-minute off blocks of rhythmic MNS stimulation (total 4 blocks)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04731714, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.