Clinical trial NCT05016765: Open-label MNS for Tourette Syndrome
Official title: Open Trial of Median Nerve Stimulation for Treatment of Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tourette Syndrome
Tic Disorder, Chronic Motor or Vocal
Keywords: Tourette
tic
Transcutaneous Electric Nerve Stimulation
Median Nerve
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2021-08-23
Enrollment: 31
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time Spent Using the Device Per Day of Use
timeFrame: At study conclusion, up to 4 weeks
measure: Time Spent Using the Device (Days Per Week)
timeFrame: At study conclusion, up to 4 weeks
measure: Plan to Continue MNS (Median Nerve Stimulation)
timeFrame: At study conclusion, up to 1 month
measure: Change in Tic Frequency With Stimulation
timeFrame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
measure: Change in Tic Intensity With Stimulation
timeFrame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
measure: Discomfort
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.
Secondary outcomes:
measure: CGI-I (Clinical Global Impression--Improvement)
timeFrame: At study conclusion, up to 4 weeks
measure: CGI Efficacy Index: Side Effects
timeFrame: At study conclusion, up to 4 weeks
measure: Mean Therapeutic Effect During Stimulator Use
timeFrame: At study conclusion, up to 4 weeks
measure: Change in Self-reported Tic Severity
timeFrame: At beginning of study participation or up to 2 weeks prior, and again at end of study participation up to 4 weeks
measure: Self-reported Duration of MNS Benefit, in Minutes
timeFrame: Monitored over the entire period of study participation, up to 4 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Movement Disorders Center
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Kevin J Black, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Evans J, Seri S, Cavanna AE. The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: a systematic review. Eur Child Adolesc Psychiatry. 2016 Sep;25(9):939-48. doi: 10.1007/s00787-016-0823-8. Epub 2016 Feb 15.
citation: Thomas R, Cavanna AE. The pharmacology of Tourette syndrome. J Neural Transm (Vienna). 2013 Apr;120(4):689-94. doi: 10.1007/s00702-013-0979-z. Epub 2013 Jan 30.
citation: Scahill L, Woods DW, Himle MB, Peterson AL, Wilhelm S, Piacentini JC, McNaught K, Walkup JT, Mink JW. Current controversies on the role of behavior therapy in Tourette syndrome. Mov Disord. 2013 Aug;28(9):1179-83. doi: 10.1002/mds.25488. Epub 2013 May 16.
citation: Lin L, Stamm K, Christidis P, APA Center for Workforce Studies. 2015 County-Level Analysis of U.S. Licensed Psychologists and Health Indicators [online]. 2016. Available at: http://www.apa.org/workforce/publications/15-county-analysis/index.aspx?tab=1 Accessed 9/29/2017.
citation: Cuenca J, Glazebrook C, Kendall T, Hedderly T, Heyman I, Jackson G, Murphy T, Rickards H, Robertson M, Stern J, Trayner P, Hollis C. Perceptions of treatment for tics among young people with Tourette syndrome and their parents: a mixed methods study. BMC Psychiatry. 2015 Mar 11;15:46. doi: 10.1186/s12888-015-0430-0.
citation: 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.