Clinical trial NCT05269953: Median Nerve Stimulation for Tourette Syndrome and Chronic Tic Disorder
Official title: A Randomised, Double-blind, Placebo-controlled, Trial of Rhythmic 10Hz Median Nerve Stimulation for the Suppression of the Urge-to-tic and Reduction of Tics in Individuals With Tourette Syndrome and Chronic Tic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tourette Syndrome
Chronic Tic Disorder
Keywords: Tourette Syndrome
Median nerve stimulation
Chronic Tic Disorder
Lead sponsor: Nottingham University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Neurotherapeutics Ltd
name: University of Nottingham
First posted: 2022-03-08
Enrollment: 132
Sex: ALL
Minimum age (years): 12
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly allocated into three groups (ratio: 1:1:1): active stimulation, sham stimulation and waitlist (no stimulation).

Those in the waitlist group would receive treatment as normal, prior to an open label phase of receiving active stimulation.
Primary purpose: TREATMENT

Brief summary: Tourette syndrome (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders that impact approximately 1% of 5-18 year olds worldwide. Both TS and CTD are characterised by the presence of tics, which are repetitive, purposeless, movements or vocalisations of short duration which can occur many times throughout a day. Tics can have a significant negative impact on daily functioning and quality of life, hence, many seek out approaches to manage and reduce their tics and the urges people with TS or CTD often feel preceding them. The two main evidence-based approaches to treating tics are behavioural therapies and medication; both of which can be effective, but accessibility and waitlists are often an issue for behavioural therapies and side effects are common with medication use. Consequently, there is an urgent need for the development of alternative, safe and accessible treatments.

This study aims to examine the effects of rhythmic pulses of electrical stimulation delivered to the wrist in treating tics in people with TS and CTD. In recent work, the investigators have shown that this type of electrical stimulation known as median nerve stimulation (MNS), can substantially reduce tics and related urges during stimulation. The investigators now want to extend this work to examine the effects of the stimulation on a higher number of people, compared to placebo and treatment as usual. The investigators will do this through assessment of symptom change using questionnaires, interviews and videos collection during four weeks of stimulation and two time points afterwards.

The investigators have developed a new MNS device for this trial which is portable and easy to use. The primary hypothesis is that active rhythmic MNS will lead to a reduction in tic severity compared to a placebo condition. The secondary hypothesis is that MNS will also have a positive beneficial effect on urges, impairment, well-being and co-occurring Obsessive-Compulsive Disorder (OCD) symptoms compared to both sham stimulation and no stimulation.

Detailed description: The symptoms of Tourette Syndrome (TS) (tics and premonitory urges) can be treated using behavioural therapies and/or medications, however access, availability, side effects and treatment resistance are factors which many people with TS and their family's express frustration with. Therefore, it is in the interest of patients and the wider medical community that alternative treatments are tested and scientifically validated. In recent work, the investigators have found that low intensity electrical stimulation delivered to the wrist can be effective in significantly reducing tics and tic related premonitory urges. In the study the investigators want to expand this work to examine the effects of the stimulation on a higher number of people, compared to placebo and treatment as usual and to examine the suitability of a wearable device for delivering stimulation from home.

The investigators will conduct a parallel, double-blind, placebo-controlled trial of a wearable, wrist-worn, therapeutic device for the suppression of premonitory urge and the reduction of tics in individuals with TS. In order to validate the device as a genuine and effective form of therapy, it is essential that a placebo branch of the study is completed. Participants will be made aware of the three different experimental arms ahead of enrolment and will be debriefed following completion of the trial. The investigators are committed to clearly explaining why a placebo condition is essential, while minimising the amount of information the investigators withhold from participants, hence the investigators feel it is important to be able to let participants know the condition participants were in at the end of the trial.

The device the investigators are aiming to trial will be programmed to deliver low-intensity (1-19 mA) rhythmic (10Hz) trains of electrical stimulation to the median nerve for 14 minutes, and will be used by each participant from home once each day, 5 days each week, for a period of 4 weeks. Participants assigned to the active condition will experience rhythmic (10Hz) trains of stimulation set to an individual intensity which the investigators have found to be effective in the investigators' previous work (-120% of intensity needed to generate a visible muscle twitch in the thenar muscle). Those assigned to the placebo group will receive stimulation at a subthreshold rate (50% intensity needed to generate thenar muscle twitch). The investigators' previous work suggests that this serves as a sufficient control condition. Those in the waitlist group would receive treatment as normal, prior to an open label phase of receiving active stimulation.

A total of 135 participants (45 per group) will be allocated to one of the three groups; active stimulation; sham stimulation; or waitlist (i.e., treatment as usual). In order to minimise the difference in age, gender and symptom severity between groups, the investigators will perform a stratified randomisation for age, gender and severity (using Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score) to allocate individuals to each group.

The effects of the stimulation will be assessed using several semi-structured interviews, questionnaire measures and video recordings of participant's tics. The investigators will also use questionnaire measures/ interviews to measure baseline characteristics of the participants, as these factors may influence response to the investigators proposed intervention. The majority of this trial will be remotely supervised and therefor the majority of these measures will also be taken through video call and online questionnaire measures with the exception of an initial visit to the University of Nottingham.

The primary hypothesis is that active MNS will lead to a reduction in tic severity compared to subthreshold placebo stimulation. The procedure for testing this will be as follows:

1. Participants who have expressed an interest in the study will be given a detailed participant information sheet. Participants will be given the opportunity to ask questions about the study. If participants wish to proceed and to have an initial telephone screening to assess eligibility participants will then be asked to complete an initial consent form which will asked for their consent to take part in the screening and for the research team to keep a record of their answers during that process.
2. Consenting participants will then be contacted by a member of the research team at an agreed time via telephone/video call. This call should last no longer than an hour. This will be used to give participants further insights into the trial and to establish trial eligibility. Trial eligibility will be assessed according to the investigators' predefined inclusion/ exclusion criteria. The YGTSS, semi structured interview will also be conducted by a trained member of the research team to establish If the potential participant has enough tics to be eligible for the trial.
3. After completing the telephone screening, eligible participants will be sent a further electronic consent form to take part in the rest of the trial. After obtaining consent, participants will be allocated into a trial arm and a date will be set for them to visit Nottingham. In the case of the wait list group participants will not visit Nottingham until participants have entered into the open label active phase of the trial.
4. During the baseline visit to the University of Nottingham, participants will receive the stimulation device and will be trained in its correct placement and use. In order to ensure participant's comfort with the stimulation, a practice session will be performed. If the participant experiences significant discomfort, participants will be withdrawn from the trial. On the same day, demographic information along with primary and secondary measures will be collected using various questionnaires and structured interviews. Participants in the waitlist group will also complete these measurements online and through video call.
5. Participants in the active and placebo groups will return home with the device and be instructed to commence stimulation sessions on the following Monday. Participants will be asked to use the device once each day, 5 days each week, for a period of 4 weeks. During the stimulation period participants will be asked to complete a few short questions each day which should take 1-2 minutes. Participants will also be contacted by a member of the research team at weeks 1, 2, 3 and 4 of stimulation and 3 and 6 months after completing stimulation. During these meetings through video call lasting approximately 1 hour various semi-structured interviews and questionnaires will be administered to assess changes in symptoms. A subset of participants will also be asked to record videos of themselves 5 minutes before the stimulation, during the stimulation and 5minutes after the stimulation and to upload these to a secure online platform. These will be used by the research team to objectively count changes in tics.

The investigators estimate that the trial will take 9 months to collect all data sets, including the 6 month follow up period. Visits to Nottingham will take place during the first 3 months of the trial.

Eligibility criteria: Inclusion Criteria:

* Aged 12 years or older. Must also be able to give informed consent (along with parents/guardians).
* Confirmed or suspected diagnosis of Tourette Syndrome or Chronic Tic Disorder with a moderate amount of tics (to be assessed during an initial screening interview).
* Stable treatment regime/no treatment for the past 2 months (i.e. if taking medication same drug \& dosage).
* Internet access \& access to electronic device to complete online questionnaires and video calls.
* Participants must be able to travel to Nottingham for one visit and have reliable access to the internet.
* Participant is willing and able to give informed consent for participation in the clinical investigation.
* Able (in the Investigators opinion) and willing to comply with all clinical investigation requirements
* Resident in the UK

Exclusion Criteria:

* Current diagnosis of epilepsy.
* Participant or participants guardian (if under 16) unable to read/write in English.
* Participants will be excluded from the trial if they find the stimulation too uncomfortable during a practice session at the in person baseline visit.
* Individuals with implanted electronic devices (e.g. pacemakers, insulin pump, implantable cardioverter defibrillator, neurostimulators).
* Individuals sharing the household with an individual with implanted electronic devices (e.g. pacemakers, insulin pump, implantable cardioverter defibrillator, neurostimulators).
* Individuals with current/ recent diagnosis or symptoms of SARS-CoV-2 will not be invited to visit the university until it is safe for them to do so (2 weeks following positive test).
* Individuals with a diagnosis of non-verbal autism or similar condition which would affect ability to give informed consent to take part in the study will not be recruited.
* Pregnant women will not be recruited for this study.
* Participants who have participated in previous research studies involving median nerve stimulation
* Participants aged over 90 years old

Primary outcomes:
measure: Change in Yale Global Tic Severity Scale - revised (YGTSS-R) total tic severity score
timeFrame: Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation
Secondary outcomes:
measure: Change in Premonitory urge for Tics Scale-Revised (PUTS-R)
timeFrame: Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation
measure: Change in Tic impairment (as measured through subscales of YGTSS-R)
timeFrame: Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation
measure: Change in Quality of life (as measured by Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QoL))
timeFrame: Baseline, week 4, and at follow-up points 3 and 6 months after starting stimulation
measure: Change in Anxiety symptoms (as measured by Becks anxiety inventory (BAI))
timeFrame: Baseline, week 4, and at follow-up points 3 and 6 months after starting stimulation
measure: Change in OCD symptoms as measured by (Children's) Yale-Brown Obsessive-Compulsive Scale ((C)Y-BOCS)
timeFrame: Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation
measure: Change in Tic frequency as quantified by analysis of video data
timeFrame: Daily during the first 2 weeks of stimulation
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Sir Colin Campbell Building
state: Nottinghamshire
Study officials:
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