Clinical Research Directory

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.

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.

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).

Neural Correlates of Sensory Phenomena in Tourette Syndrome

The most pervasive sensory manifestation of TS is sensory over-responsivity (SOR). SOR is defined as excessive behavioral response to commonplace environmental stimuli. SOR is an integral but poorly understood facet of the TS phenotype, one intertwined with core elements of the disorder and worse QOL. This proposal seeks to clarify the mechanistic bases of SOR in TS. Adults with with TS will be recruited 1) to complete a standardized clinical symptom assessment battery and 2) to undergo electroencephalogram (EEG), autonomic, and audio-visual monitoring during tactile and auditory stimuli paradigms, as well as at rest.

Sensorimotor and Psychosocial Trajectories in Adolescents With Tic Disorder

Individuals with tic disorders have lower quality of life, sensory and movement difficulties, and poorer mental, social, and physical health compared to the general population. Current clinical care for individuals with tic disorders is limited: no interventions are proven to prevent or stop the disorder exist, and most treatments focus solely on tics, though other symptoms often affect quality of life more than tics. To develop new treatments and improve care for people with tics, researchers need to better understand the different symptoms people experience and how the brain causes these symptoms. Many individuals with tic disorders have sensory and movement symptoms other than tics. A common sensory symptom is increased sensitivity to common sensations, such as glare from sunlight, tags in shirt collars, and noises from passing cars. A common movement symptom is poor handwriting and/or poor coordination. In one study of adolescents with tic disorder, difficulty with hand coordination predicted tic severity 7.5 years later, suggesting that sensory and/or motor difficulties may be a risk factor for more severe tics later in life. Despite how common they are, much is unknown about sensory and motor difficulties experienced by people with tic disorders. Additionally, most studies of people with tics enroll younger children. As a result, little is known about sensory, motor, and psychosocial development in adolescents with tics. Knowledge of sensory and motor difficulties in adolescents with tics is important to understand because, in other adolescent populations, such difficulties are associated with worse mental and social health and worse quality of life. Deepening insight into the sensory, motor, and psychosocial development of adolescents with tic disorders is crucial to identify causes and risk factors for poor health in this population. The goals of this study are to measure sensory and motor symptoms and function in adolescents with tics and to compare them to adolescents without tics. The research team will enroll adolescents with tics and adolescents without tics to participate in the study. Adolescent participants will complete questionnaires, electroencephalogram (EEG) tasks, and other sensory and motor tasks at baseline (with 2 study visits occurring within 30 days of each other) and 2 years later (again, with 2 study visits, occurring within 30 days of each other). A parent or other adult who knows the adolescent well will also complete questionnaires as part of the study.

Where Wild Things Grow: Nature- and Activity-based Group Interventions for Neurodivergent Children and Youth

The goal of this action research project is to develop and implement nature- and activity-based group interventions across health care, school and leisure settings in Southern Norway. The interventions are tailored to support the mental health, self-efficacy and daily life functioning of children and youth in the Agder region, with a particular focus on youngsters who struggle due to neurodivergence, such as Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) or Tourette's syndrome. The main questions we aim to answer are: 1. To what extent does nature- and activity-based outdoor education contribute to improvements in children's quality of life? 2. To what extent does nature- and activity-based interventions in a health care setting improve children's self-efficacy, self-esteem and quality of life? 3. Is there a difference in physiological reactions between nature-based provision of education or therapy and traditional indoor provision of education or therapy? Participants will take part in a 12-week school-based or health care intervention.

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.

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.

Strengthening Tourette Treatment OPtions Using TMS to Improve CBIT, a Double-blind, Randomized, Controlled Study

This pilot study will investigate the clinical and neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) followed by comprehensive behavioral intervention for tics (CBIT) in adult patients with Tourette's Syndrome (TS). Two groups of moderate disease severity will be randomized to receive active or sham rTMS targeted to the supplementary motor area (SMA) followed by eight CBIT sessions. The change in tic frequency and severity (primary outcome) and neurophysiological changes (secondary outcome) will be compared between the two groups. The central hypothesis is that low frequency rTMS will augment the effects of CBIT through favorable priming of the SMA network.

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

Cognitive-psychophysiological Treatment for Tics in Young People With Tourette's Syndrome With or Without Biofeedback

The goal of this clinical trial is to compare the effectiveness of CoPs therapy with or without the therapeutic component of biofeedback in treating tics in Tourette Syndrome with emerging young adults. Hypotheses: 1. The CoPs+Biofeedback treatment will improve the severity of tics (YGTSS) and the Clinical Global Impression, surpassing the clinical significance threshold of CoPs treatment alone. 2. We expect that the identified variables (psychosocial, neurocognitive, biological) will predict the improvement of tics. Researchers will compare if the biofeedback treatment will improve the severity of tics. * In the pre-test, participants will undergo two interviews, each lasting 3 hours. These interviews will assess (through a battery of tests) the severity of tics as well as the psychosocial, biological, and neurocognitive aspects of functioning. A general assessment of intelligence and executive functions will also be conducted. * They will next attend 10 to 12 therapy sessions, with or without biofeedback. (The biofeedback component is explained in more detail in the ''Study Design'' section). * The post-test follow-ups consist of two evaluations: one 3 months after the end of the treatment and the other 6 months after. The evaluation will be done using the same battery of tests as during the pre-test interview.

Multitarget Stereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome

The goal of this clinical trial is to investigate the neural mechanisms underlying Tourette syndrome (TS) and see if personalized deep brain stimulation (DBS) can help reduce tics in TS patients and improve related issues like anxiety, attention problems, and obsessive-compulsive behaviors. In this study, researchers will use stereoelectroencephalography (SEEG) and electrocorticography (ECoG) to record brain activity in key areas involved in movement and emotion, including the nucleus accumbens (NAc), anterior limb of the internal capsule (ALIC), insular cortex, anterior cingulate cortex (ACC), central medial thalamic nucleus (CM), globus pallidus internus (GPi), and motor cortex (M1). They will test stimulation in these areas to evaluate acute therapeutic effect for each target and to identify a new effective new target. Later, participants will receive DBS treatment under three different conditions, each for 1 month to identify the optimal target: 1. Stimulation at the new target, 2. Stimulation at the CM, 3. Sham stimulation (does not actually stimulate). Finally, DBS will be continued at the optimal target for an additional three months to confirm its therapeutic impact. By analyzing the brain activity and comparing these conditions, the study will clarify the neural mechanisms underlying TS and learn which target works best to lower tics and improve overall quality of life for TS patients.

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.

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).

Multimodal Electrophysiological Study of Cortico-subcortical Biomarkers of Tics in Tourette Syndrome

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the occurrence of involuntary movements (motor tics) and vocalizations (phonic tics). The onset of TS is usually in childhood, and the prevalence of TS is estimated between 0.3 and 0.9% before the age of 18, decreasing progressively after that age. Most patients also suffer from associated psychiatric comorbidities (ADHD, OCD, mood disorders). Although the cause of TS remains unknown, the preferred hypothesis is the interaction of predisposing genetic factors and precipitating environmental factors (perinatal accidents, infectious diseases). From a pathophysiological point of view, it is widely demonstrated by structural, electrophysiological studies, functional neuroimaging, as well as by different animal models, that dysfunctions of the cortico-striato-pallido-thalamo-cortical loops (responsible for the regulation of movements, cognitive processes, and emotions) play a major role in the genesis of tics. Deep brain stimulation (DBS) treatment can be proposed as an invasive therapy in patients with severe TS resistant to usual treatments (psychotherapy, pharmacological treatments). In a well-selected population of drug-resistant patients, DBS allows an estimated overall improvement of 30 to 50% in the YGTSS score. The deep brain stimulation method currently used in TS is based on continuous (24/7) and undifferentiated stimulation (fixed electrical intensity). This stimulation paradigm, devoid of adaptability to the patient's symptoms, could be at the origin of undesirable effects (related to the modulation of physiological signals), of a sub-optimal efficiency, or of an unnecessary overuse of the stimulator's capacities (battery depletion). The development of new deep brain stimulation paradigms ("closed-loop stimulation"), allowing the identification of pathological neuronal activity and the dynamic adaptation of stimulation parameters to these neuronal signals, requires reliable and reproducible pathological biomarker, correlated with the occurrence of tics. However, in TS, electrophysiological abnormalities are still not well characterized, and most of the work published on the subject were based on intraoperative recordings and needs to be confirmed on recordings at a distance from the surgery before its potential use in closed-loop stimulation paradigms. Indeed, during the first weeks after surgery, different factors tend to modify the electrophysiological signals. Several questions arise at the end of this healing period: * Are these pathological oscillations (distinct from the brain oscillations induced by physiological voluntary movement) still detectable weeks after the surgery? * What are the temporal dynamics of these oscillations around a tic? * What is the spatial topography of these oscillations within the GPi? * Is there a strong inter-individual variability? * How are changes in cortical activity associated with these subcortical oscillations? * Are the modulations of pallidal activity alone sufficient to predict the occurrence of a tic? Thus, our study aims to define precisely the cortico-subcortical activity concomitant with the occurrence of a tic, and to identify reliable and reproducible biomarker(s) associated with tics in TS. In order to specify these biomarker(s), their temporal correlation to tic occurrence, their spatial distribution, as well as the dynamics and cortico-subcortical coherence of the identified abnormalities, we propose a prospective study on 10 patients with severe and drug-resistant TS, treated by bi-pallidal deep brain stimulation as part of routine care (no device implantation as part of the research). An evaluation of pallidal LFP synchronized with a high-resolution video-electroencephalography recording (128 to 256 sensors) will be performed at a distance (M+\[3-48\]) from surgery, in order to determine the variations in pallidal and electroencephalographic activity surrounding the occurrence of tics. A control condition with voluntary ("tic-like") movement will be carried out in a second time, to distinguish the modifications related to the voluntary movement from those related to the occurrence of a tic. A reconstruction of the electrode positioning will be performed using the LeadDBS pipeline, and individual and group analyses will be performed to specify the mapping of pathological oscillations within the pallidum and throughout the cerebral cortex.

Effect of RNS in Treatment-refractory Tourette's Syndrome

The study is to investigate the effect of personalized responsive neurostimulation (RNS) therapy guided by stereoelectroencephalography (SEEG) in patients with treatment-resistant Tourette's Syndrome (TR-TS).