Clinical trial NCT06361004: Exploring DBS Efficacy in Treatment-refractory Tourette's Syndrome
Official title: Investigating the Impact of Deep Brain Stimulation (DBS) in Treatment-refractory Tourette's Syndrome (TR-TS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Tourette's Syndrome
Keywords: TS, DBS
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2024-04-11
Enrollment: 60
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 primary purpose of this study is to investigate the effect of deep brain stimulation (DBS) in patients with Treatment-refractory Tourette's syndrome (TR-TS) implantation targeting the Antero-medial globus pallidus interna (GPi), Antero-medial globus pallidus interna (amGPi), Postero-ventrolateral GPi (pvGPi), Centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus (Cm-Spv-Voi), Centre median nucleus and nucleus ventro-oralis (Cm-Voi), or Nucleus Accumbens/ Anterior Limb of Internal Capsule (NA-ALIC), or other unreported nuclei targets.

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. Males are more commonly affected than females, and there is a broad spectrum of symptom severity. Treatment-refractory Tourette's Syndrome (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 DBS has the most potential for TR-TS with apparent symptoms. The stimulation targets of DBS for patients with obsessive-compulsive disorder include GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, and NA-ALIC. However, the DBS case reports are limited and lack high-quality, evidence-based medical evidence. So, this cohort study focuses on the effectiveness of DBS-targeted GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, NA-ALIC, or other unreported nuclei targets on TR-TS.

Another goal of this program 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. This separate study is an option and will not affect current study participation.

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 and will not affect current study participation.

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 6 months
timeFrame: Baseline to 6 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, and 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)
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: