Clinical trial NCT06889480: Multitarget Stereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome
Official title: MultitArget STereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tourette Syndrome
Deep Brain Stimulation
Keywords: Tourette syndrome
Electrophysiology
Tics
Psychiatric Comorbidities
Deep Brain Stimulation
Biomarker
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2025-03-21
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change in Yale Global Tic Severity Scale (YGTSS) Score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Secondary outcomes:
measure: Change in Modified Rush Video Rating Scale (MRVRS)
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Premonitory Urge Scale (PUTS) Score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Conners' Adult ADHD Rating Scale (CAARS) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Hamilton Anxiety Scale (HAMA) Score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Hamilton Depression Scale (HAMD) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Young Mania Rating Scale (YMRS) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Mini-Mental State Examination (MMSE) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Change in Montreal Cognitive Assessment Beijing Version (MoCA) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: change in Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL) score
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
measure: Incidence of Treatment-Related Adverse Events
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Other outcomes:
measure: New Stimulation Target Identification
timeFrame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Jianguo Zhang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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