Open-label MNS for Tourette Syndrome

Sponsor

Washington University School of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT05016765

Collaborator

(none)

Enrollment

Location

Arm

5.3

Actual Duration (Months)

6.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome Tic Disorder, Chronic Motor or Vocal	Device: Active, self-directed electrical stimulation of the median nerve	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

All participants will receive MNS at 12 Hz, pulse width 200µs. After initial threshold determination and training on device usage, individual participants will choose duration and intensity of treatment depending on their momentary symptom severity and history of response to treatment.All participants will receive MNS at 12 Hz, pulse width 200µs. After initial threshold determination and training on device usage, individual participants will choose duration and intensity of treatment depending on their momentary symptom severity and history of response to treatment.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Trial of Median Nerve Stimulation for Treatment of Tourette Syndrome

Actual Study Start Date :

Nov 18, 2021

Actual Primary Completion Date :

Apr 27, 2022

Actual Study Completion Date :

Apr 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active MNS 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). Other Names: Rhythmic MNS

Arm

Intervention/Treatment

Experimental: Active MNS

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).

Other Names:

Rhythmic MNS

Outcome Measures

Primary Outcome Measures

Time spent using the device [At study conclusion, up to 1 month]
Minutes used over the four-week period
Plan to continue MNS [At study conclusion, up to 1 month]
Answer (yes / no / maybe) to the question, "Do you expect to continue to use the stimulator?"
Change in tic frequency with stimulation [Up to one month]
Change in self-reported tic frequency on a 0-5 scale adapted from the Yale Global Tic Severity Scale (YGTSS) from the beginning to the end of each stimulation period
Change in tic intensity with stimulation [Up to one month]
Change in self-reported tic intensity on a 0-5 scale adapted from the YGTSS from the beginning to the end of each stimulation period
Discomfort [Up to one month]
Mean discomfort while using the stimulator (0-3 scale adapted from the Clinical Global Impression - Improvement [CGI-I] Efficacy Index), reported at the end of each stimulation period
Relationship to blinded study results: frequency [At study conclusion, up to 1 month]
Correlation of change in tic frequency during this study as in Outcome 3 above with change in tic frequency during active, rhythmic stimulation during the RCT
Relationship to blinded study results: intensity [At study conclusion, up to 1 month]
Correlation of change in tic intensity during this study as in Outcome 4 above with change in tic intensity during active, rhythmic stimulation during the RCT

Secondary Outcome Measures

CGI Efficacy Index: therapeutic effect [At study conclusion, up to 1 month]
Overall impact of the stimulation on symptoms throughout the study period
CGI Efficacy Index: side effects [At study conclusion, up to 1 month]
Overall discomfort from stimulation throughout the study period
Mean therapeutic effect during stimulator use [Up to 1 month]
Mean self-rated therapeutic effect (from the modified CGI Efficacy Index) when device is on, reported twice daily in response to a text message, if the stimulator is on when the text is received
Change in self-reported tic severity [At study conclusion, up to 1 month]
Self-rated tic severity over the past week using the Adult Tic Questionnaire, first rating at (or within 2 weeks prior to) the beginning of the study and second rating at the end of study participation
Self-reported duration of MNS benefit, in minutes [At study conclusion, up to 1 month]
Participant response to the question "How long do you think the improvement in your tics lasted after you turned off the device?"

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Completed participation in the study called "Peripheral induction of inhibitory brain circuits to treat Tourette's: pilot"
Informed consent by adult participant, or assent by child and informed consent by guardian

Exclusion Criteria:

Has an implanted device that could be affected by electrical current
Pregnancy known to participant or (for children) to the parent
Severe or unstable systemic illness
Factors (such as exaggerated symptom report) that in the judgment of the principal investigator may make the outcome measures inaccurate
Judged by investigator to be unlikely to complete study procedures