Clinical trial NCT06785532: Effect of RNS in Treatment-refractory Tourette's Syndrome
Official title: Investigating the Effect of Responsive Neurostimulation (RNS) in Patients with Treatment-refractory Tourette's Syndrome (TR-TS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tourette Syndrome
Keywords: TS, RNS
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2025-01-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with Treatment-refractory Tourette's syndrome (TR-TS)
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by repetitive, involuntary movements and vocalizations known as tics. It typically manifests in childhood and may persist into adulthood. The prevalence of TS varies globally, affecting approximately 1% of the population. There is a broad spectrum of symptom severity. Treatment-refractory TS (TR-TS) refers to cases where standard therapeutic interventions, such as behavioural therapy and medications, have shown limited effectiveness. TR-TS prevalence is relatively lower but highlights the challenges in managing severe and persistent symptoms. In a comprehensive survey of diverse neuromodulation therapies, targeting specific nuclei with personalized responsive neurostimulation (RNS) has the most potential for TR-TS with apparent symptoms. However, the RNS case reports are limited and lack high-quality, evidence-based medical evidence. The stimulation targets of RNS for patients with TS include GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, and NA-ALIC. While stereoelectroencephalography (SEEG) brain mapping can help identify Individualized effective targets and stimulation parameters. So, this cohort study focuses on the effectiveness of SEEG-guided RNS on TR-TS patients. Another goal is to study the neuronal activity of the GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, and NA-ALIC, or other unreported nuclei targets, respectively. At the same time, some subjects are presented with a task involving an unexpected reward and different cognitive tasks.

Some participants will also be invited to join a related study that involves positron emission tomography (PET) scanning to determine how the stimulation changes activity in the brain. Participation in the separate PET study is optional.

Eligibility criteria: Inclusion Criteria:

1. aged 18-65;
2. able to provide written informed consent;
3. have a diagnosis of Tourette's syndrome according to the Statistical Manual of Mental Disorders-Fourth Edition-Text Revised (DSM-IV-TR) criteria and confirmed by the Mini-International Neuropsychiatric Interview Chinese version 5.0;
4. with a YGTSS of at least 35 for at least 12 months before surgery, while YGTSS- Total Motor≥15;
5. must have failed conventional medical treatment at adequate therapeutic doses of three classes of medication lasting for at least three months;
6. must not be suitable for behavioural intervention or that this intervention is inappropriate or unsuccessful;
7. have been on stable comorbid conditions without suicidal ideation for at least six months.

Exclusion Criteria:

1. presence of other psychotic disorders;
2. have a treatment history that includes electroconvulsive therapy (ECT), modified electroconvulsive therapy (MECT), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), DBS, and transcranial magnetic stimulation (TMS);
3. presents a suicide risk (defined as a HAMD-17 score of ≥3 on suicide-related items);
4. experience difficulty in effectively communicating with investigators;
5. with a history of traumatic brain injury (TBI);
6. with intracranial or cardiovascular stents;
7. substance abuse within the past six months;
8. unstable neurological or coagulation disorders;
9. women who are pregnant, lactating, or of childbearing potential who refuse the use of reliable contraception during the study;
10. have been involved in other clinical studies within three months before enrollment in this study;
11. any conditions considered by the study group.

Primary outcomes:
measure: Yale Global Tic Severity Scale (YGTSS): Reduction in total tics on the YGTSS after 12 months
timeFrame: Baseline to 12 months post-surgery
Secondary outcomes:
measure: YGTSS-Total Motor: Change in YGTSS-Total Motor at week 2, month 3, month 6, and month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: YGTSS-Total Phonic: Change in YGTSS-Total phonic at week 2, month 3, month 6, and month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: YGTSS: remission.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: YGTSS: response rate.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Yale-Brown Obsessive Compulsive Scale (Y-BOCS): Change in Y-BOCS at week 2, month 3, month 6, and month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Hamilton Anxiety Scale (HAMA): the change from baseline to 2 weeks, 3 months, 6 months, and 12 months in the HAMA total score.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Hamilton Depression Rating Scale (HAMD-17): the changes of HAMD-17 scores and its subscales from baseline to 2 weeks, 3 months, 6 months, and 12 months.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Pittsburgh Sleep Quality Index (PSQI): the change of PSQI from baseline to Week 2, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Clinical Global Impression-Severity (CGI-S): the change from baseline to 2 weeks, 3 months, 6 months, and 12 months in Clinical Global Impression-Severity (CGI-S) Remove
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Clinical Global Impression-Improvement (CGI-I): CGI-I score at Week 2, Month 1, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: EuroQol-5 Dimension-level Scale (EQ-5D-5L): the change from baseline to Week 2, Month 3, Month 6, and Month 12 in EQ-5D-5L.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Young Mania Rating Scale (YMRS): the change from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Safety as indicated by the number of Adverse Events: Week 2, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Change from baseline in the Verbal Fluency Test (COWAT)
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the Trailmaking Test A&B
timeFrame: 1 year after neurostimulator implantation.
measure: Change in Rey-Osterrieth Complex Figure Test
timeFrame: 1 year after neurostimulator implantation.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Hongxing Wang, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References: