Open Trial of Median Nerve Stimulation for Treatment of Tourette Syndrome
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Tourette Syndrome
- Sponsor
- Washington University School of Medicine
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Time Spent Using the Device (Days Per Week)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Kevin J. Black, M.D.
Principal Investigator
Washington University School of Medicine
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
Outcomes
Primary Outcomes
Time Spent Using the Device (Days Per Week)
Time Frame: At study conclusion, up to 4 weeks
Number of days per week the device was used
Plan to Continue MNS (Median Nerve Stimulation)
Time Frame: At study conclusion, up to 1 month
Answered yes (from options yes / no / maybe) to the question, "Do you expect to continue to use the stimulator?"
Time Spent Using the Device Per Day of Use
Time Frame: 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
Change in Tic Frequency With Stimulation
Time Frame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
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 .
Change in Tic Intensity With Stimulation
Time Frame: Recorded every time the device was turned on and every time it was turned off, up to 4 weeks
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.
Discomfort
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.
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.
Secondary Outcomes
- Self-reported Duration of MNS Benefit, in Minutes(Monitored over the entire period of study participation, up to 4 weeks)
- CGI Efficacy Index: Side Effects(At study conclusion, up to 4 weeks)
- Mean Therapeutic Effect During Stimulator Use(At study conclusion, up to 4 weeks)
- CGI-I (Clinical Global Impression--Improvement)(At study conclusion, up to 4 weeks)
- Change in Self-reported Tic Severity(At beginning of study participation or up to 2 weeks prior, and again at end of study participation up to 4 weeks)