Multitarget Stereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome (MASTERS-TS)

Capital Medical University

Status: Enrolling

Conditions: Tourette Syndrome; Deep Brain Stimulation

Treatments: Device: CM-DBS; Device: Sham Stimulation; Device: New Target DBS

Study type: Interventional

Funder types: Other

Identifiers

NCT06889480

HX-B-2024057

Details and patient eligibility

About

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.

Enrollment: 5 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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5 participants in 3 patient groups

New Target DBS

Experimental group

Description:

Participants in this arm will receive active deep brain stimulation targeted to a novel brain region. The new target is identified through electrophysiological brain mapping and 24-hour stimulation. Stimulation parameters (frequency, voltage, pulse width) will be individually optimized based on mapping results.

Treatment:

Device: New Target DBS

CM-DBS

Active Comparator group

Description:

Participants in this arm will receive active deep brain stimulation at the central medial thalamic nucleus (CM), a well-established target for TS treatment. Stimulation settings are determined during electrophysiological brain mapping and 24-hour stimulation. This arm serves as the active comparator, enabling the evaluation of relative efficacy and safety between the conventional CM target and the new target intervention.

Treatment:

Device: CM-DBS

Sham Stimulation

Sham Comparator group

Description:

Participants in this arm will undergo identical surgical procedures and follow-up assessments as in the active stimulation arms but will receive sham (inactive) stimulation. This arm is designed to control for placebo effects and ensure that any observed improvements in TS symptoms are attributable to the active interventions.

Treatment:

Device: Sham Stimulation