Tourette SyndromeMASTERS-TSNCT06889480
Multitarget Stereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome
A study testing New Target DBS and CM-DBS in people with Tourette Syndrome and Deep Brain Stimulation, run by Beijing Tiantan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Tourette Syndrome, Deep Brain Stimulation
- What is being tested?
- New Target DBS and CM-DBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2024to Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 and 60 years.
- Diagnosis of Tourette Syndrome according to DSM-V criteria, defined as:
- The presence of multiple motor tics and at least one vocal tic at some point (not necessarily simultaneous).
- Tics that have persisted for more than 1 year from their onset.
- Onset of tics occurring before the age of 18.
- The disorder is not attributable to the physiological effects of a substance or another medical condition.
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- 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.
- Inadequate response to conservative treatments (standard pharmacological and behavioral therapy).
- Disease duration of more than 1 year.
- Any coexisting medical, neurological, or psychiatric disorders have been treated and remain stable for at least 6 months.
- A stable psychosocial environment.
- Neuropsychological evaluation demonstrating that the candidate can tolerate the surgical procedure, postoperative follow-up, and potential adverse events.
- The participant, or his/her legal representative, is able to provide written informed consent.
Who cannot join
- Presence of suicidal risk, defined as a score of ≥3 on the suicide-related items of the Hamilton Depression Rating Scale (HAMD).
- History of drug or alcohol dependence within the past 6 months.
- Abnormal brain structure as indicated by CT or MRI scans.
- Presence of any condition that could lead to surgical failure or interfere with postoperative management.
- Diagnosis of factitious disorder, malingering, or psychogenic tics.
- Contraindications to neurosurgical procedures (e.g., history of cerebral infarction, hydrocephalus, cerebral atrophy, or post-stroke sequelae).
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- Contraindications for CT/MRI scanning (e.g., claustrophobia).
- Pregnancy or lactation, or a positive pregnancy test prior to randomization.
- Contraindications to general anesthesia (e.g., severe arrhythmia, severe anemia, hepatic or renal dysfunction).
- Expected survival of less than 12 months.
- Participation in other interventional clinical studies that may influence outcome assessments.
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Jianguo Zhang, M.D., Ph.D., +86 13601294613, zjguo73@126.com
About this study
Official title: MultitArget STereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome
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.
Read more
Later, participants will receive DBS treatment under three different conditions, each for 1 month to identify the optimal target:
- Stimulation at the new target,
- Stimulation at the CM,
- 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.
- Conditions
- Tourette Syndrome, Deep Brain Stimulation
- Being tested
- New Target DBS, CM-DBS, Sham Stimulation
- Keywords
- Tourette syndrome, Electrophysiology, Tics, Psychiatric Comorbidities, Deep Brain Stimulation, Biomarker
- Medical subject headings
- Tourette Syndrome, Tics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
New Target DBSDevice
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.
CM-DBSDevice
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.
Sham StimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| New Target DBS | Experimental | 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. Receives: Device: New Target DBS |
| CM-DBS | Active comparator | 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. Receives: Device: CM-DBS |
| Sham Stimulation | Sham comparator | 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. Receives: Device: Sham Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Yale Global Tic Severity Scale (YGTSS) Score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Secondary outcomes (12)
Change in Modified Rush Video Rating Scale (MRVRS)
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Premonitory Urge Scale (PUTS) Score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Conners' Adult ADHD Rating Scale (CAARS) score
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
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Hamilton Anxiety Scale (HAMA) Score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Hamilton Depression Scale (HAMD) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Young Mania Rating Scale (YMRS) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Columbia Suicide Severity Rating Scale (C-SSRS)
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Mini-Mental State Examination (MMSE) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Montreal Cognitive Assessment Beijing Version (MoCA) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
change in Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL) score
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Incidence of Treatment-Related Adverse Events
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.
Measured: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2025
- Study start1 Oct 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Tourette SyndromeStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianguo Zhang, Beijing Tiantan Hospital
- Investigators
- Jianguo Zhang, M.D., Ph.D., Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06889480
- Sponsor's protocol ID
- HX-B-2024057
- Acronym
- MASTERS-TS
- Status last verified
- Mar 2025
- First submitted
- 16 Mar 2025
- Last updated
- 22 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Martinez-Ramirez D, Jimenez-Shahed J, Leckman JF, Porta M, Servello D, Meng FG, Kuhn J, Huys D, Baldermann JC, Foltynie T, Hariz MI, Joyce EM, Zrinzo L, Kefalopoulou Z, Silburn P, Coyne T, Mogilner AY, Pourfar MH, Khandhar SM, Auyeung M, Ostrem JL, Visser-Vandewalle V, Welter ML, Mallet L, Karachi C, Houeto JL, Klassen BT, Ackermans L, Kaido T, Temel Y, Gross RE, Walker HC, Lozano AM, Walter BL, Mari Z, Anderson WS, Changizi BK, Moro E, Zauber SE, Schrock LE, Zhang JG, Hu W, Rizer K, Monari EH, Foote KD, Malaty IA, Deeb W, Gunduz A, Okun MS. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurol. 2018 Mar 1;75(3):353-359. doi: 10.1001/jamaneurol.2017.4317.
PubMed 29340590Muller-Vahl KR, Szejko N, Saryyeva A, Schrader C, Krueger D, Horn A, Kuhn AA, Krauss JK. Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome. Brain Stimul. 2021 May-Jun;14(3):662-675. doi: 10.1016/j.brs.2021.04.004. Epub 2021 Apr 18.
PubMed 33857664Schuller T, Gruendler TOJ, Smith EE, Baldermann JC, Kohl S, Fischer AG, Visser-Vandewalle V, Ullsperger M, Kuhn J, Huys D. Performance monitoring in obsessive-compulsive disorder: Insights from internal capsule/nucleus accumbens deep brain stimulation. Neuroimage Clin. 2021;31:102746. doi: 10.1016/j.nicl.2021.102746. Epub 2021 Jun 29.
PubMed 34229156Xiong B, Li B, Wen R, Gao Y, Gong F, Li D, Xu Y, Deng H, Xiao L, Yin S, Zhang W, Lozano AM, Wang W. Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder. J Neurosurg. 2023 May 26;139(5):1376-1385. doi: 10.3171/2023.4.JNS221824. Print 2023 Nov 1.
PubMed 37243560McGovern RA, Sheth SA. Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery. J Neurosurg. 2017 Jan;126(1):132-147. doi: 10.3171/2016.1.JNS15601. Epub 2016 Apr 1.
PubMed 27035167O'Neill J, Piacentini JC, Peterson BS. Cingulate role in Tourette syndrome. Handb Clin Neurol. 2019;166:165-221. doi: 10.1016/B978-0-444-64196-0.00011-X.
PubMed 31731911Jackson SR, Sigurdsson HP, Dyke K, Condon M, Jackson GM. The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. J Neuropsychol. 2021 Sep;15(3):340-362. doi: 10.1111/jnp.12242. Epub 2021 Mar 27.
PubMed 33774919Jackson SR, Loayza J, Crighton M, Sigurdsson HP, Dyke K, Jackson GM. The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. Cortex. 2020 May;126:119-133. doi: 10.1016/j.cortex.2019.12.021. Epub 2020 Jan 22.
PubMed 32070809Neumann WJ, Huebl J, Brucke C, Lofredi R, Horn A, Saryyeva A, Muller-Vahl K, Krauss JK, Kuhn AA. Pallidal and thalamic neural oscillatory patterns in tourette's syndrome. Ann Neurol. 2018 Oct;84(4):505-514. doi: 10.1002/ana.25311. Epub 2018 Oct 4.
PubMed 30112767Gunduz A, Okun MS. A Review and Update on Tourette Syndrome: Where Is the Field Headed? Curr Neurol Neurosci Rep. 2016 Apr;16(4):37. doi: 10.1007/s11910-016-0633-x.
PubMed 26936259Cagle JN, Okun MS, Opri E, Cernera S, Molina R, Foote KD, Gunduz A. Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit. J Neurol Neurosurg Psychiatry. 2020 May;91(5):533-539. doi: 10.1136/jnnp-2019-321973. Epub 2020 Mar 5.
PubMed 32139653Bohlhalter S, Goldfine A, Matteson S, Garraux G, Hanakawa T, Kansaku K, Wurzman R, Hallett M. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain. 2006 Aug;129(Pt 8):2029-37. doi: 10.1093/brain/awl050. Epub 2006 Mar 6.
PubMed 16520330Wang Z, Maia TV, Marsh R, Colibazzi T, Gerber A, Peterson BS. The neural circuits that generate tics in Tourette's syndrome. Am J Psychiatry. 2011 Dec;168(12):1326-37. doi: 10.1176/appi.ajp.2011.09111692. Epub 2011 Sep 28.
PubMed 21955933Johnson KA, Duffley G, Foltynie T, Hariz M, Zrinzo L, Joyce EM, Akram H, Servello D, Galbiati TF, Bona A, Porta M, Meng FG, Leentjens AFG, Gunduz A, Hu W, Foote KD, Okun MS, Butson CR. Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Oct;6(10):961-972. doi: 10.1016/j.bpsc.2020.11.005. Epub 2020 Nov 24.
PubMed 33536144Johnson KA, Fletcher PT, Servello D, Bona A, Porta M, Ostrem JL, Bardinet E, Welter ML, Lozano AM, Baldermann JC, Kuhn J, Huys D, Foltynie T, Hariz M, Joyce EM, Zrinzo L, Kefalopoulou Z, Zhang JG, Meng FG, Zhang C, Ling Z, Xu X, Yu X, Smeets AY, Ackermans L, Visser-Vandewalle V, Mogilner AY, Pourfar MH, Almeida L, Gunduz A, Hu W, Foote KD, Okun MS, Butson CR. Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study. J Neurol Neurosurg Psychiatry. 2019 Oct;90(10):1078-1090. doi: 10.1136/jnnp-2019-320379. Epub 2019 May 25.
PubMed 31129620
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MultitArget STereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome
- ClinicalTrials.gov ID
- NCT06889480
- Acronym / sponsor ID
- MASTERS-TS / HX-B-2024057
- Conditions
- Tourette Syndrome, Deep Brain Stimulation
- Keywords
- Tourette syndrome, Electrophysiology, Tics, Psychiatric Comorbidities, Deep Brain Stimulation, Biomarker
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 21 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Stimulation at the new target,
- Stimulation at the CM,
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| New Target DBS | Experimental | Device: New Target DBSParticipants 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. |
| CM-DBS | Active comparator | Device: CM-DBSParticipants 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. |
| Sham Stimulation | Sham comparator | Device: Sham StimulationParticipants 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Age between 18 and 60 years.
- Diagnosis of Tourette Syndrome according to DSM-V criteria, defined as:
- 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.
- Inadequate response to conservative treatments (standard pharmacological and behavioral therapy).
- Disease duration of more than 1 year.
Key exclusion criteria (12 listed)
- Presence of suicidal risk, defined as a score of ≥3 on the suicide-related items of the Hamilton Depression Rating Scale (HAMD).
- History of drug or alcohol dependence within the past 6 months.
- Abnormal brain structure as indicated by CT or MRI scans.
- Presence of any condition that could lead to surgical failure or interfere with postoperative management.
- Diagnosis of factitious disorder, malingering, or psychogenic tics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| New Target DBSParticipants 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. | Device | New Target DBS |
| CM-DBSThis 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. | Device | CM-DBS |
| Sham StimulationParticipants 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. | Device | Sham Stimulation |
Primary outcome
Change in Yale Global Tic Severity Scale (YGTSS) Score
Time frame: 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.
12 secondary outcomes
Change in Modified Rush Video Rating Scale (MRVRS)
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Premonitory Urge Scale (PUTS) Score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Conners' Adult ADHD Rating Scale (CAARS) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Hamilton Anxiety Scale (HAMA) Score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Hamilton Depression Scale (HAMD) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Young Mania Rating Scale (YMRS) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Mini-Mental State Examination (MMSE) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Change in Montreal Cognitive Assessment Beijing Version (MoCA) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
change in Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL) score
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Incidence of Treatment-Related Adverse Events
Time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Background: PubMed 29340590Martinez-Ramirez D, Jimenez-Shahed J, Leckman JF, Porta M, Servello D, Meng FG, Kuhn J, Huys D, Baldermann JC, Foltynie T, Hariz MI, Joyce EM, Zrinzo L, Kefalopoulou Z, Silburn P, Coyne T, Mogilner AY, Pourfar MH, Khandhar SM, Auyeung M, Ostrem JL, Visser-Vandewalle V, Welter ML, Mallet L, Karachi C, Houeto JL, Klassen BT, Ackermans L, Kaido T, Temel Y, Gross RE, Walker HC, Lozano AM, Walter BL, Mari Z, Anderson WS, Changizi BK, Moro E, Zauber SE, Schrock LE, Zhang JG, Hu W, Rizer K, Monari EH, Foote KD, Malaty IA, Deeb W, Gunduz A, Okun MS. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurol. 2018 Mar 1;75(3):353-359. doi: 10.1001/jamaneurol.2017.4317.
- Background: PubMed 33857664Muller-Vahl KR, Szejko N, Saryyeva A, Schrader C, Krueger D, Horn A, Kuhn AA, Krauss JK. Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome. Brain Stimul. 2021 May-Jun;14(3):662-675. doi: 10.1016/j.brs.2021.04.004. Epub 2021 Apr 18.
- Background: PubMed 34229156Schuller T, Gruendler TOJ, Smith EE, Baldermann JC, Kohl S, Fischer AG, Visser-Vandewalle V, Ullsperger M, Kuhn J, Huys D. Performance monitoring in obsessive-compulsive disorder: Insights from internal capsule/nucleus accumbens deep brain stimulation. Neuroimage Clin. 2021;31:102746. doi: 10.1016/j.nicl.2021.102746. Epub 2021 Jun 29.
- Background: PubMed 37243560Xiong B, Li B, Wen R, Gao Y, Gong F, Li D, Xu Y, Deng H, Xiao L, Yin S, Zhang W, Lozano AM, Wang W. Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder. J Neurosurg. 2023 May 26;139(5):1376-1385. doi: 10.3171/2023.4.JNS221824. Print 2023 Nov 1.
- Background: PubMed 27035167McGovern RA, Sheth SA. Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery. J Neurosurg. 2017 Jan;126(1):132-147. doi: 10.3171/2016.1.JNS15601. Epub 2016 Apr 1.
- Background: PubMed 31731911O'Neill J, Piacentini JC, Peterson BS. Cingulate role in Tourette syndrome. Handb Clin Neurol. 2019;166:165-221. doi: 10.1016/B978-0-444-64196-0.00011-X.
- Background: PubMed 33774919Jackson SR, Sigurdsson HP, Dyke K, Condon M, Jackson GM. The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. J Neuropsychol. 2021 Sep;15(3):340-362. doi: 10.1111/jnp.12242. Epub 2021 Mar 27.
- Background: PubMed 32070809Jackson SR, Loayza J, Crighton M, Sigurdsson HP, Dyke K, Jackson GM. The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. Cortex. 2020 May;126:119-133. doi: 10.1016/j.cortex.2019.12.021. Epub 2020 Jan 22.
- Background: PubMed 30112767Neumann WJ, Huebl J, Brucke C, Lofredi R, Horn A, Saryyeva A, Muller-Vahl K, Krauss JK, Kuhn AA. Pallidal and thalamic neural oscillatory patterns in tourette's syndrome. Ann Neurol. 2018 Oct;84(4):505-514. doi: 10.1002/ana.25311. Epub 2018 Oct 4.
- Background: PubMed 26936259Gunduz A, Okun MS. A Review and Update on Tourette Syndrome: Where Is the Field Headed? Curr Neurol Neurosci Rep. 2016 Apr;16(4):37. doi: 10.1007/s11910-016-0633-x.
- Background: PubMed 32139653Cagle JN, Okun MS, Opri E, Cernera S, Molina R, Foote KD, Gunduz A. Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit. J Neurol Neurosurg Psychiatry. 2020 May;91(5):533-539. doi: 10.1136/jnnp-2019-321973. Epub 2020 Mar 5.
- Background: PubMed 16520330Bohlhalter S, Goldfine A, Matteson S, Garraux G, Hanakawa T, Kansaku K, Wurzman R, Hallett M. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain. 2006 Aug;129(Pt 8):2029-37. doi: 10.1093/brain/awl050. Epub 2006 Mar 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jianguo Zhang, M.D., Ph.D. principal investigator
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing New Target DBS and CM-DBS in people with Tourette Syndrome and Deep Brain Stimulation, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hutao Xie, M.D., Ph.D. (+8618756921517, xieht0123@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Yale Global Tic Severity Scale (YGTSS) Score (time frame: administered at baseline, 1 month after each randomized stimulation period during the crossover phase, and 3 months after continuous optimal stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06889480, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.