Deep Brain Stimulation, Tourette Syndrome
Conditions
Keywords
Tourette syndrome, Electrophysiology, Tics, Psychiatric Comorbidities, Deep Brain Stimulation, Biomarker
Brief summary
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.
Interventions
DEVICENew Target DBS
Participants in this arm will receive active DBS targeting a novel brain region identified via electrophysiological brain mapping. A DBS electrode will be implanted at the new target, and stimulation parameters (including frequency, voltage, and pulse width) are individually optimized based on mapping and 24-hour testing. The procedure is performed using a robotic system for precise electrode placement, and the device is provided by Beijing PINS Medical Co., Ltd.
DEVICECM-DBS
This intervention involves active DBS at the central medial thalamic nucleus (CM) -a widely used target in TS treatment. A DBS electrode is implanted at the CM target, with stimulation settings determined through electrophysiological brain mapping and subsequent 24-hour stimulation. This arm serves as an active comparator, with stimulation administered during a 1-month period in the crossover phase. The same device and robotic-assisted implantation are used to ensure consistency and precision.
DEVICESham Stimulation
Participants assigned to the sham stimulation arm undergo the identical surgical procedure and electrode implantation as those in the active arms. However, during the stimulation periods, the device is programmed to deliver no active stimulation. This sham intervention is designed to control for placebo effects and ensure that any observed improvements in TS symptoms are attributable to the active DBS interventions.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants are blinded to the stimulation condition (i.e., whether they receive new target stimulation, CM-DBS, or sham stimulation), and the outcomes assessors are also blinded to the intervention assignments. However, due to the nature of the procedure, care providers and investigators are not masked.
Intervention model description
This study employs a randomized crossover design. In the initial phase, each participant is randomly assigned to receive one of three different stimulation interventions - new target stimulation, CM-DBS, and sham stimulation - each for one month in a randomized order. Following this phase, the best target stimulation and short-term efficacy parameters are individually re-optimized for an additional three months to evaluate long-term efficacy. This design allows each participant to serve as their own control, thereby reducing inter-subject variability and improving the precision of treatment comparisons. Outcome measures, including tic severity and standard neuropsychiatric assessments, are administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 60 years. 2. Diagnosis of Tourette Syndrome according to DSM-V criteria, defined as: i. The presence of multiple motor tics and at least one vocal tic at some point (not necessarily simultaneous). ii. Tics that have persisted for more than 1 year from their onset. iii. Onset of tics occurring before the age of 18. iv. The disorder is not attributable to the physiological effects of a substance or another medical condition. 3. A Yale Global Tic Severity Scale (YGTSS) total score greater than 35 (on a scale of 0-50) for at least 1 year, with a motor tic score of ≥15, and tics being the primary cause of disability. 4. Inadequate response to conservative treatments (standard pharmacological and behavioral therapy). 5. Disease duration of more than 1 year. 6. Any coexisting medical, neurological, or psychiatric disorders have been treated and remain stable for at least 6 months. 7. A stable psychosocial environment. 8. Neuropsychological evaluation demonstrating that the candidate can tolerate the surgical procedure, postoperative follow-up, and potential adverse events. 9. The participant, or his/her legal representative, is able to provide written informed consent.
Exclusion criteria
1. Presence of suicidal risk, defined as a score of ≥3 on the suicide-related items of the Hamilton Depression Rating Scale (HAMD). 2. History of drug or alcohol dependence within the past 6 months. 3. Abnormal brain structure as indicated by CT or MRI scans. 4. Presence of any condition that could lead to surgical failure or interfere with postoperative management. 5. Diagnosis of factitious disorder, malingering, or psychogenic tics. 6. Contraindications to neurosurgical procedures (e.g., history of cerebral infarction, hydrocephalus, cerebral atrophy, or post-stroke sequelae). 7. Contraindications for CT/MRI scanning (e.g., claustrophobia). 8. Pregnancy or lactation, or a positive pregnancy test prior to randomization. 9. Contraindications to general anesthesia (e.g., severe arrhythmia, severe anemia, hepatic or renal dysfunction). 10. Expected survival of less than 12 months. 11. Participation in other interventional clinical studies that may influence outcome assessments. 12. Any other condition that, in the investigator's judgment, renders the candidate unsuitable for participation or poses a significant risk (e.g., inability to understand study procedures or poor adherence).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Yale Global Tic Severity Scale (YGTSS) Score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The YGTSS is a 10-item semi-structured clinician-rating instrument that evaluates motor and phonic symptoms' number, frequency, intensity, complexity, and interference. The items about the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. The Total Tic Severity Score ranges from 0-50, with a higher score indicating a higher severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Scale (HAMD) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Hamilton Depression Scale (HAMD) is used to assess the severity of depressive symptoms, with total scores ranging from 0 to 52. Higher scores indicate more severe depression. Evaluations will occur at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the HAMD score indicates an improvement in depressive symptoms. |
| Change in Modified Rush Video Rating Scale (MRVRS) | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Modified Rush Video Rating Scale (MRVRS) is a validated, video-based instrument for objectively assessing tic severity in patients with Tourette Syndrome. The MRVRS evaluates motor and phonic tics using a revised scoring method that captures tic frequency, intensity, and complexity from a 5-minute video recording. The MRVRS ranges from 0-20, with a higher score indicating a higher severity of symptoms. In this study, trained, blinded evaluators will rate each participant's tic severity using the MRVRS at multiple time points. Assessments are performed at baseline, after 1 month of stimulation during each randomized crossover period (following New Target DBS Stimulation, CM DBS Stimulation, and Sham Stimulation), and again after 3 months of continuous optimal stimulation. A decrease in the MRVRS score from baseline will indicate an improvement in tic severity. |
| Change in Premonitory Urge Scale (PUTS) Score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Premonitory Urge Scale (PUTS) is a self-reported measure that evaluates the intensity of premonitory urges preceding tics in patients with Tourette Syndrome. The PUTS score ranges from 9-36, where higher values reflect more severe urges, will be recorded at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. Changes in the PUTS score will indicate alterations in the severity of premonitory urges. |
| Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a clinician-rated instrument that assesses the severity of obsessive-compulsive disorder (OCD). Scores range from 0 (no symptoms) to 40 (severe symptoms). Assessments will be performed at baseline, after each 1-month randomized stimulation phase (following New Target DBS, CM DBS, and Sham stimulation), and after 3 months of continuous optimal stimulation. A reduction in the Y-BOCS score indicates an improvement in OCD symptoms. |
| Change in Conners' Adult ADHD Rating Scale (CAARS) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Conners' Adult ADHD Rating Scale (CAARS) will be used to evaluate the severity of attention deficit hyperactivity disorder (ADHD) , including inattention, hyperactivity, and impulsivity. The scale provides a score reflecting overall ADHD severity. Assessments will be conducted at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A decrease in the CAARS score indicates improvement in ADHD symptoms |
| Change in Hamilton Anxiety Scale (HAMA) Score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Hamilton Anxiety Scale (HAMA) is a clinician-rated scale used to assess the severity of anxiety symptoms, with scores ranging from 0 to 56. Higher scores indicate greater anxiety. HAMA assessments will be performed at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the HAMA score reflects a decrease in anxiety symptoms. |
| Change in Columbia Suicide Severity Rating Scale (C-SSRS) | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Columbia Suicide Severity Rating Scale (C-SSRS) primarily evaluates the presence, severity, and frequency of suicidal ideation and behaviors rather than providing a single numerical range. Typically, higher scores indicate greater suicide risk, with severity rated individually per item rather than summed into a total score. The C-SSRS will be administered at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the C-SSRS score indicates an improvement in suicidal risk. |
| Change in Mini-Mental State Examination (MMSE) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Mini-Mental State Examination (MMSE) is a clinician-administered test that evaluates overall cognitive function. The MMSE provides a score ranging from 0 to 30, with lower scores indicating greater cognitive impairment. In this study, trained evaluators will assess the MMSE score at baseline, 3 months post-intervention, and 6 months post-intervention. The primary measure is the change in the MMSE score from baseline, which will reflect any improvement or decline in cognitive function due to the interventions. |
| Change in Montreal Cognitive Assessment Beijing Version (MoCA) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Montreal Cognitive Assessment Beijing Version (MoCA) is a brief screening tool that evaluates multiple cognitive domains, including memory, executive function, attention, language, and visuospatial abilities. The MoCA yields a total score from 0-30, with lower scores indicating more significant cognitive deficits. In this study, the MoCA will be administered by trained evaluators at baseline, 3 months post-intervention, and 6 months post-intervention. The outcome measure is the change in the MoCA score from baseline, which will help determine the effect of the interventions on cognitive performance. |
| change in Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | Quality of life will be evaluated using the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL), a patient-reported measure that assesses the impact of TS on daily functioning and overall well-being. The scale yields a total score ranging from 0-108 where lower scores indicate a better quality of life. Assessments will be performed at baseline, after each 1-month randomized stimulation phase during the crossover period, and following 3 months of continuous optimal stimulation. A decrease in the GTS-QOL score from baseline indicates an improvement in quality of life. |
| Incidence of Treatment-Related Adverse Events | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | Safety will be evaluated by recording the incidence, severity, and nature of treatment-related adverse events (AEs), including surgical complications, stimulation-related side effects, and device-related issues. Data will be collected at every follow-up visit and monitored throughout the study. This measure will provide an overall safety profile of the interventions. |
| Change in Young Mania Rating Scale (YMRS) score | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | The Young Mania Rating Scale (YMRS) is a clinician-administered instrument assessing the severity of manic symptoms, with scores ranging from 0 to 60. Higher scores indicate more severe mania. YMRS evaluations will be performed at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the YMRS score signifies an improvement in manic symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| New Stimulation Target Identification | administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation | This outcome measure assesses the effectiveness of electrophysiological brain mapping (using SEEG) in identifying a novel stimulation target. Success is defined as the reliable identification of a new target based on electrophysiological criteria during brain mapping and subsequent 24-hour stimulation. The proportion of patients with a successfully identified new target will be determined. |
Countries
China
Contacts
Primary ContactHutao Xie, M.D., Ph.D.
Outcome results
None listed