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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 2
- 主要终点
- Change in Yale Global Tic Severity Scale - revised (YGTSS-R) total tic severity score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The member of the research team performing allocation will not be involved in the collection or processing of measurement outcomes (questionnaire/ video data). This same researcher will also be responsible for assigning participants to interventions by programming the MNS devices to deliver sham/active stimulation. This member of the research team will be responsible for creating and maintaining a document which links each participants unique ID with the condition they have been assigned to.
All other members of the research team, participants and legal guardians will be blind to sham/active group allocation. Participants in the waitlist group and their carers will not be blind to the group they have been allocated to. Participants allocated to the waitlist group will not be blind to the stimulation type they will receive (i.e., all participants initially allocated to the waitlist group will go on to receive active rhythmic MNS at the conclusion of their participation).
入排标准
- 年龄范围
- 12 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Sham stimulation
干预措施: Sham stimulation (Device)
Active stimulation
干预措施: Active stimulation (Device)
Waitlist (no stimulation)
Treatment as usual.
结局指标
主要结局
Change in Yale Global Tic Severity Scale - revised (YGTSS-R) total tic severity score
时间窗: Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation
The primary outcome measure will be the scores from our core measures of tic severity (using scores from YGTSS-R). The YGTSS-R total tic severity score range from 0-50, where higher scores indicate a worse outcome. These will be used to assess any change in tic severity symptoms between groups and over the initial 4 week stimulation period.
Change in Yale Global Tic Severity Scale - Revised (YGTSS-R) Total Tic Severity Score
时间窗: Baseline and week 4 after starting stimulation
The primary outcome measure were the scores from our core measures of tic severity (using scores from YGTSS-R). The YGTSS-R total tic severity score ranges from 0-50, where higher scores indicate a worse outcome. These were used to assess any change in tic severity symptoms between groups and over the initial 4 week stimulation period. YGTSS-R is recognised as the gold standard measure for evaluating tic severity in Tourette syndrome.
次要结局
- Change in OCD symptoms as measured by (Children's) Yale-Brown Obsessive-Compulsive Scale ((C)Y-BOCS)(Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation)
- Change in Premonitory urge for Tics Scale-Revised (PUTS-R)(Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation)
- Change in Anxiety symptoms (as measured by Becks anxiety inventory (BAI))(Baseline, week 4, and at follow-up points 3 and 6 months after starting stimulation)
- Change in Tic impairment (as measured through subscales of YGTSS-R)(Baseline, week 1, 2, 3 and 4, and at follow-up points 3 and 6 months after starting stimulation)
- Change in Quality of life (as measured by Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QoL))(Baseline, week 4, and at follow-up points 3 and 6 months after starting stimulation)
- Change in Tic frequency as quantified by analysis of video data(Daily during the first 2 weeks of stimulation)
- Change in Tic Frequency as Quantified by Analysis of Video Data(Pre-stimulation period and During stimulation period)
- Change in Premonitory Urge (as Measured by Premonitory Urge for Tics Scale-Revised (PUTS-R))(Baseline and week 4 after starting stimulation)
- Change in Symptoms of Obsessive-Compulsive Disorder (OCD) (as Measured by (Children's) Yale-Brown Obsessive-Compulsive Scale (C)Y-BOCS)(Baseline and week 4 after starting stimulation)