Clinical Research Directory

Evaluating and Promoting Resilience in Adolescents With Tourette Syndrome

This study adapts and tests PRISM (Promoting Resilience in Stress Management), a short skills-based program that teaches resilience, for teens ages 12-18 with Tourette syndrome or persistent tic disorder. The study has three parts. First, a small group of teens and their caregivers try PRISM and give feedback to adapt it for teens with tics. Second, 15 teens complete the adapted program to see whether it is practical and acceptable. Third, 60 teens are randomly assigned to PRISM plus usual care or usual care alone, to see whether a larger trial is feasible and to get early information on resilience and other outcomes.

Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Tic Disorders/Tourette's Syndrome in Children and Adolescents

The objective of this trial is to evaluate the effect of transcutaneous auricular vagus nerve stimulation compared to sham stimulation in improving chronic tic disorder or Tourette's syndrome in children and adolescents.

Safety of Cultured Allogeneic Adult Umbilical Cord or Placental Derived Mesenchymal Stem Cells for Tourette Syndrome

This trial will study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord or placental derived mesenchymal stem cells for the treatment of Tourette Syndrome

Evaluation of an Online Comprehensive Behavioral Intervention for Tics (CBIT) Therapist Training Program

Tic disorders are a class of childhood-onset neuropsychiatric disorders that occur in 1-3% of the population. Studies have shown that a non-drug treatment known as Comprehensive Behavioral Intervention for Tics (CBIT) is more effective than supportive therapy for reducing tics in children and adults. Although CBIT is now recommended as a first-line intervention for tic disorders, many patients do not have access to CBIT, in part due to a lack of trained therapists. Currently, the only option available for training therapists in CBIT is an intensive, two day, in-person behavior therapy training institute (BTTI). This study will compare the traditional in-person training approach to a recently developed online, self-paced CBIT therapist training program called CBIT-Trainer with regard to (1) therapists' ability to accurately administer CBIT and (2) change in the severity of patients' tic symptoms after being treated by a CBIT-trained therapist.

Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression

The investigators will implant and monitor 8 research subjects with a subcortical closed-loop system for detection and suppression of tics in subjects with medically refractory debilitating Tourette Syndrome. The project will use the FDA-approved "Medtronic Percept PC" device, which is an implantable neurostimulator capable of recording neural signals. The study will target the CM nucleus of the thalamus and the aGPi in each brain hemisphere from each subject and we will connect the two leads placed in each brain hemisphere to two Percept devices.

Epidiolex in Obsessive Compulsive Disorder and Related Disorders

The primary objective of the proposed study is to evaluate the safety and efficacy of Epidiolex (cannabidiol) in adults with obsessive compulsive and related disorders (OCRDs). Subjects will be treated in an open-label fashion with Epidiolex for two weeks.

Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders

There are currently no approved medications for the treatment of anxiety in children and youth with neurodevelopmental disorders (NDDs), both common and rare. Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs. More research is needed to confirm whether or not sertraline could help improve anxiety in children and youth with common and rare neurodevelopmental conditions. This is a pilot study, in which we plan to estimate the effect size of reduction in anxiety of sertraline vs. placebo. across rare and common neurodevelopmental disorders, and determine the best measure(s) to be used as a primary transdiagnostic outcome measure of anxiety, as well as diagnosis specific measures in future, larger-scale clinical trials of anxiety in NDDs.

Multimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics

Tourette Syndrome and Persistent Motor/Vocal Tic Disorder affect 1-3% of youth and can be associated with impaired functioning, emotional and behavioral problems, physical pain, diminished quality of life, and peer victimization. Chronic tics are the primary symptom. Comprehensive Behavioral Intervention for Tics (CBIT) is a manualized treatment focused on tic management skills. During the core CBIT procedure, competing response training, patients learn to inhibit tics by engaging in a competing motor action. The overall objective of this study is to identify bio-behavioral predictors and correlates of response and the most potent aspects of CBIT. Participants with chronic tics will complete a manualized course of 8-session CBIT. Neural, behavioral, psychosocial, and global functioning will be assessed longitudinally to examine predictors and correlates of response. CBIT sessions will be video recorded. CBIT process will be measured with a video-based behavioral coding scheme that will be refined and validated during years 1-2 using archival CBIT videos

A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder

The primary objective of this study is to evaluate the long-term safety and tolerability of ecopipam tablets in children (greater than or equal to \[\>=\] 6 and less than \[\<\] 12 years of age), adolescents (\>=12 and \<18 years of age), and adults (\>=18 years of age) with Tourette's Syndrome (TS).

Trajectories of Change in Tourette Syndrome

This K23 Career Development Award is designed to provide the training needed for the PI to achieve her long-term career goal of conducting independent, programmatic intervention research in developmental populations. The training will emphasize gaining expertise in higher-intensity, multi-method, within-subject data collection and analysis. This award builds on the PI's emerging experience in tic disorders and pediatric behavioral interventions, and her ability to quickly learn and apply advanced statistical methods. The award will extend the PI's training through the following short-term training goals: 1) multi-method data collection and integration (electronic momentary assessment \[EMA\], wearable devices, neurocognitive tasks), 2) leading and designing pediatric clinical trials, 3) managing and analyzing large, multilevel datasets, and 4) career development and contribution to the field. The PI has developed a training plan to accomplish these goals in concert with her mentors, a team of leading experts in the fields of psychiatry and psychology, who will closely monitor training through regular meetings. The highly structured training plan also includes a set of formal coursework and workshops for each training goal to complement the hands-on experience the PI will gain from leading the research project. The objective of this proposal is to comprehensively map symptom change across time and during a behavioral intervention for youth with Persistent Tic Disorders (PTDs). PTDs affect approximately 1% of the population, can cause significant disability, have high rates of comorbidity, and are associated with a four-fold increase in suicide risk. Research has established that tic symptoms and their change over time are highly idiographic. However, first-line, evidence-based, existing interventions are "one-size-fits-all," and are only effective for 60% of patients. The current study aims to use advanced statistical methods and a novel theoretical framework to map the stability of tic patterns, along with systemic factors that relate to tic change over time. Study hypotheses, based on the literature and preliminary data, are that a) tic change patterns will be stable before intervention for all participants, b) disruption of stable patterns during the intervention phase will be associated with treatment response, and c) this disruption will depend on the specific driver of tic symptoms pre-intervention. N = 30 youth ages 12-17 with chronic tics will be recruited for the study. There will be three study phases: 1) pre-intervention (4 weeks), 2) intervention (8 weeks), and 3) post-intervention (4 weeks). Before and between each phase, participants will complete 4 traditional assessments to assess symptoms and treatment response. Throughout the 16 weeks of the study, we will collect EMA data focused on factors relevant to tics (4x per day), physiological data from wearable devices (passive, continuous), and neurocognitive task performance and tic video observation (1x per week). Results will inform efforts to develop individualized interventions for individuals with PTDs to improve treatment outcomes.

Transcranial Ultrasound Stimulation for Tourette Syndrome

This is a phase 1 clinical trial investigating the use of low-energy Transcranial Ultrasound Stimulation (TUS) to treat Tourette Syndrome (TS). Objectives and Background. TS is a neurodevelopmental condition marked by motor and vocal tics that often resist standard pharmacological or behavioral treatments. Current neuromodulation options like Deep Brain Stimulation (DBS) are invasive, while non-invasive methods like TMS lack the precision to reach deep brain structures. The study aims to: 1. Evaluate tolerability: Assess TUS safety in older adolescents and adults with TS. 2. Test efficacy: Compare TUS at the intralaminar thalamic nuclei (CM/Pf/Voi) and the supplementary motor area (SMA) against a sham treatment to see if it reduces tic frequency and severity. 3. Optimize protocols: Determine if dual-target or multiple-session stimulation is more effective than single-target or single-session protocols. TUS uses low energy, pulsed, focused ultrasound to induce transient neuromodulatory responses lasting up to 60 minutes. TUS can precisely target deep structures like the thalamus. Study Methods * Design: A phase 1, double-blind, crossover trial. * Participants: 20 individuals (ages 16+) with a diagnosis of TS and significant tic severity (YGTSS score \> 22 or sub-score \> 15). * Procedure: Participants receive four different modalities over four separate weeks, with 7-day washouts: * TUS of the CM/Pf/Voi only. * TUS of the SMA only. * Combined TUS of both targets. * Sham TUS. * Evaluation: The primary endpoint is the percent change on the Rush Video-Based Tic Rating Scale (RVBTRS). Secondary measures include the Yale Global Tic Severity Scale (YGTSS) and the Premonitory Urges for Tics Scale (PUTS). Because TUS requires extreme precision to hit deep brain targets, every participant undergoes a comprehensive imaging protocol using a 3T GE UHP scanner. * Mapping the Targets: We use Diffusion Tensor Imaging (DTI) and Tractography to locate the specific "wiring" of the individual's brain. This allows to find: * The CM/Pf/Voi (Centromedian-parafascicular complex) in the thalamus. * The SMA (Supplementary Motor Area) in the cortex. * Precision Imaging: High-resolution 1 mm-isotropic T1-weighted, T2-weighted, and Zero Echo Time (ZTE) images are used. ZTE is particularly important as it helps the BabelBrain software account for the thickness and density of the skull, which can deflect ultrasound waves. * Real-Time Tracking: During the actual stimulation, the team uses a Brainsight neuro-navigation system. This acts like a GPS, using the patient's MRI "map" to ensure the ultrasound transducer is perfectly aligned with the target. Innovation This is the first human study to apply TUS to TS patients. By targeting both deep and cortical regions independently or simultaneously, the researchers aim to modulate the "network-level" connectivity implicated in tic generation. Technical Ultrasound Parameters The study uses a custom 128-element phased-array transducer (Sonic Concepts H317) to deliver TUS. * Core Settings: * Frequency: 250 kHz. * Intensity: spatial-peak pulse-average intensity (ISPPA) of 10 W/cm2 * Targeting \& Safety: * BabelBrain Software: Calculates real-time acoustic simulations to correct for bone aberrations and ensure the Mechanical Index (MI) stays below 1.9 and thermal rise remains under 2°C. * Electronic Steering: Allows the focal spot to be moved without physically repositioning the device, enabling coverage of large areas like the SMA or deep structures like the CM/Pf/Voi complex. * Biological Protocols: * Inhibitory: pulse repetition frequency (PRF), 10% duty cycle, lasting 120 seconds. * Excitatory: "theta burst" PRF, 10% duty cycle, lasting 80 seconds. Clinical Assessment Criteria The trial employs three main scales to capture both objective tic data and subjective patient experiences: 1. Rush Video-Based Tic Rating Scale (RVBTRS): * The Primary Measure: This is the only validated tool that provides an objective assessment by analyzing 10-minute video recordings. * Method: Two blinded evaluators count tics and rate their severity across two views: a close-up (head/shoulders) and a full-body frontal view. * Focus: It specifically measures the patient's ability to actively inhibit tics during the recording. 2. Yale Global Tic Severity Scale (YGTSS): * The Gold Standard: A clinician-rated interview that assesses symptoms over the prior 7-10 days. * Scoring: It rates motor and phonic tics separately on five dimensions: number, frequency, intensity, complexity, and interference. * Baseline Requirement: To participate in the trial, patients must have a total tic severity score of at least 22 (or a sub-score of 15). 3. Premonitory Urges for Tics Scale (PUTS): * Self-Report: A 9-item questionnaire where patients rate the intensity of pre-tic sensations (like pressure, itchiness, or tension) on a scale of 1 to 4. * Interpretation: Scores range from 9 to 36; higher scores reflect more distressing urges.

Median Nerve Stimulation for Tourette Syndrome and Chronic Tic Disorder

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.

Role of Frontal Cortex in the Pathophysiology of Gilles de la Tourette Syndrome (GTS)

Tourette's syndrome (TS) is a debilitating and severe syndrome whose pathophysiology remains unclear. In order to precise the cortical regions involved in the generation of tics, investigators will realize an electroencephalogram (EEG) recording in the frontal cortex of TS patients in ecological conditions (EEG-holter). Activity changes will be correlated with event markers of tics and neurovegetative parameters. Statistical analyses will be compared between epochs of EEG recording with tics and without tics. The aim is to define the cortical regions involved in the genesis of tics in order to consider new targets for cortical stimulation.

CBIT+TMS R33 Phase

Chronic tics are a disabling neuropsychiatric symptom associated with multiple child-onset mental disorders. Chronic tics affect 1-3% of youth 1 and are associated with impaired functioning, emotional and behavioral problems, physical pain, diminished quality of life, peer victimization, and a fourfold increased risk of suicide compared to the general population. Large randomized trials have demonstrated the superiority of CBIT over supportive therapy in child and adult patients. However, in these trials, only 52% of children and 38% of adults showed clinically meaningful tic improvement, meaning that 50-60% of patients do not benefit from CBIT. CBIT success relies on an ability to suppress tics that many youth lack. The central aim of CBIT is to enhance voluntary tic suppression. Better tic suppression ability drives CBIT improvement 10 and predicts lower tic burden over the course of illness. During the core CBIT procedure, competing response training, patients learn to inhibit tics by engaging in a competing motor action. However, research shows that many youth lack this fundamental tic suppression ability that CBIT aspires to enhance. This study will examine the clinical and neural effects of a treatment combining Comprehensive Behavioral Intervention for Tics (CBIT) and transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA) in young people with tic disorder.

Remote Delivery of a Mindfulness-based Intervention for Tics

This research study is being done to compare a mindfulness-based intervention for tics (MBIT) to psychoeducation with relaxation and supportive therapy (PRST) for individuals with Tourette's syndrome or Persistent Tic Disorders (collectively TS). It is the investigator's hope that this information cam be used to improve current treatments for individuals with TS.

Longitudinal Impact of Stressors in Adults With Tourette Syndrome

The Investigators propose a two-year, longitudinal pilot study of TS adults (\>18) to determine impact of lifetime environmental stress exposure on tic severity, psychiatric comorbidity severity, and health-related quality of life (HRQOL).

SCI-110 in the Treatment of Tourette Syndrome

To evaluate the efficacy, safety and tolerability of the cannabinoid-based medication SCI-110 compared to placebo in subjects with Tourette syndrome.

A Multicenter Pediatric Deep Brain Stimulation Registry

There is limited data on outcomes for children who have undergone deep brain stimulation (DBS) for movement disorders, and individual centers performing this surgery often lack sufficient cases to power research studies adequately. This study aims to develop a multicenter pediatric DBS registry that allows multiple sites to share clinical pediatric DBS data. The primary goals are to enable large-scale, well-powered analyses of the safety and efficacy of DBS in the pediatric population and to further explore and refine DBS as a therapeutic option for children with dystonia and other hyperkinetic movement disorders. Given the current scarcity of evidence available to clinicians, this centralized multicenter repository of clinical data is critical for addressing key research questions and improving clinical practice for pediatric DBS.

Sensory Symptoms in Tourette Syndrome

Patients with tics will be asked to complete a series of validated questionnaires (in electronic and/or paper format) regarding symptoms and conditions often associated with Tourette syndrome, including premonitory urges, sensory experiences, inattention, obsessive-compulsive tendencies, anxiety, and depression. Participants will also be asked to complete a quality of life assessment. This series of questionnaires will be administered annually.

Efficacy and Safety of Gemlapodect (NOE-105) in Adults and Adolescents With Tourette Syndrome

This study is designed to evaluate the efficacy and safety of gemlapodect (NOE-105) on reducing tics associated with Tourette Syndrome (TS) in adults with TS. Adolescents will be enrolled after a sentinel cohort of adults is complete.

Observational Database on Deep Brain Stimulation in Tourette Syndrome

Within an ongoing deep brain stimulation (DBS) program for Tourette syndrome (TS) at the Department of Neurology, Pitié-Salpêtrière Hospital, Paris/France, the investigator team plans to evaluate patients pre-operatively and then at one year intervals post-operatively until the 5-year mark has been achieved. The investigator team will investigate tic severity, psychiatric co-morbidities, quality of life, and neuropsychological measures.

Characterising Sleep Disorders in Children With Tourette Syndrome

Healthy sleep is essential for a young person's growth, development, and wellbeing. It is estimated that up to 80% of young people with Tourette Syndrome experience sleep difficulties. Tourette Syndrome is a neurological condition that causes sudden, unwanted, and repeated motor movements and vocal sounds, known as tics. Previous studies have shown that children with this condition have poorer sleep quality, specifically increased awakenings and difficulties falling or staying asleep. These challenges highlight the need to better understand sleep problems in young people with Tourette Syndrome. This study will assess whether children's tics affect their sleep quality by measuring how often tics occur during sleep and how severe they are. To do this, the investigators will use a new Tic index to measure the impact of tics during an overnight sleep study. A watch like device that tracks movement and light levels will also be employed to help estimate when someone is asleep or awake. Together, these measures enable a clear comparison between the sleep of children with Tourette Syndrome and those without. Children will also complete a questionnaire to gain insights into their personal experiences and how they perceive tics to influence their sleep. The specific objectives include: 1. Compare the sleep patterns of children with Tourette syndrome (TS) to those of children without TS, to see whether tics are linked to any differences in sleep. 2. Assess how accurately the tic measurements identify tics during sleep, to see whether they could be useful in future research. 3. Explore whether tic activity changes during different stages of sleep in children with TS. 4. Look at how the results from sleep recordings (such as movement monitors and tic measurements) relate to questionnaire responses about sleep and tics. Results from this study can be used to support future research that continues to improve the management and treatment of sleep problems in Tourette Syndrome children.

Epidemiology of Assertiveness and Emotion Management Disorders in People With Tourette's Syndrome

The goal of this study is to evaluate the proportion of assertiveness difficulties in Tourette syndrome. Participants will complete several e-questionnaires (on assertiveness, Tourette severity, quality of life, self-esteem and comorbidities like depression, anxiety...).

Outcomes of Cognitive Behavioral Therapy (CBT) Interventions Provided by Unlicensed Professionals

To examine the effectiveness and clinical care outcomes of cognitive-behavioral therapy interventions at Massachusetts General Hospital (MGH).