Deep Brain Stimulation in Tourette Syndrome

NCT06388291 | Completed DMC

• 1 other identifier: CTU/2018/321
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Op-TICS is a clinical investigation of the use of Deep Brain Stimulation (DBS), with a CE marked implantable device, to reduce severe motor and vocal tics in patients who suffer from Tourette Syndrome (TS). It is a randomised, double-blind, crossover clinical investigation for 20 patients. Op-TICS will be performed at the National Hospital for Neurology \& Neurosurgery. Following DBS surgery, participants will first enter an open adjustment phase, of 6 months, where the electrical stimulation settings of the device are optimised. Participants will then enter the double-blind phase that will include successively up to 2 weeks with stimulation on and up to 2 weeks with the stimulation off in a randomised order. The primary outcome measure is the tic severity score measured by the Yale Global Tic Severity Scale -Total Tic Score after two weeks OFF-stimulation versus two weeks ON-stimulation in the double-blind randomised crossover phase

Conditions

Tourette Syndrome; Deep Brain Stimulation

Keywords

Movement Disorders; Nervous System Diseases; Brain Diseases; Functional Disorder

Outcome Measures

Primary Outcomes (1)

• Tic severity score measured by the YGTSS-TTS (total tic) after two weeks OFF-stimulation versus two weeks ON-stimulation in the double-blind randomised crossover phase

  To assess whether GPi DBS is effective in reducing severe motor or vocal tics, measured with the Yale Global Tic Severity Scale -Total Tic Severity (YGTSS- TTS) two weeks OFF stimulation vs two weeks ON Stimulation at the end of the double blind randomised crossover blinded phase, i.e., Effect 1 (Visit 5) vs Effect 2 (Visit 7)

  4 weeks

Secondary Outcomes (9)

• MRVRS at the end of the OFF-stimulation state versus the end of the ON-stimulation state in the blinded, randomised crossover phase.

  4 weeks

• Change in the MRVRS between baseline 0 and the end of the open-phase (Baseline 1)

  24 weeks

• Change in the YGTSS (global) between baseline 0 and the end of the open-phase (Baseline 1)

  24 weeks

• Change in the GTS-QOL questionnaire measures at baseline 0 and the end of the open-phase (Baseline 1)

  24 weeks

• Change in the YBOCS between baseline 0 and the end of the open-phase (Baseline 1)

  24 weeks

Study Arms (2)

ON/OFF-stimulation

EXPERIMENTAL

This group will have the stimulator switched on for two weeks followed by off for two weeks

Device: Deep Brain Stimulation

OFF/ ON -stimulation

EXPERIMENTAL

This group will have the stimulator switched off for two weeks followed by on for two weeks

Device: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

ON/OFF stimulation vs OFF/ON stimulation

OFF/ ON -stimulation; ON/OFF-stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients aged 18 and over:
• with chronic, severe, treatment refractory Tourette Syndrome, as defined by a Yale Global Tic Severity Scale score (YGTSS (global)) \>50/100
• with failure to respond to a minimum of two antipsychotic drugs prescribed separately at maximally tolerated doses for a minimum of 6 weeks OR, intolerance of these medications causing early cessation due to adverse events
• who have provided agreement to participate and written informed consent

You may not qualify if:

• Schizophrenia or other primary psychotic disorder (schizophrenia (ICD11 6A20); delusional disorders (ICD11 6A24); schizoaffective disorder (ICD11 6A21).
• History of substance-induced psychotic disorder (ICD11 6C40.6 Alcohol-induced psychotic disorder; ICD11 6C43.6 Opioid-induced psychotic disorder; ICD11 6C41.6 Cannabis-induced psychotic disorder; ICD11 6C42.6 Synthetic cannabinoid-induced psychotic disorder; ICD11 6C44.6 Sedative, hypnotic or anxiolytic-induced psychotic disorder; ICD11 6C45.6 Cocaine-induced psychotic disorder; ICD11 6C46.6 Stimulant-induced psychotic disorder including amphetamines, methamphetamine or methcathinone; ICD11 6C47.6 Synthetic cathinone-induced psychotic disorder; 6C49.5 Hallucinogen-induced psychotic disorder; ICD11 6C4B.6 Volatile inhalant-induced psychotic disorder; ICD11 6C4C.6 MDMA or related drug-induced psychotic disorder, including MDA; ICD11 6C4D.5 Dissociative drug-induced psychotic disorder including Ketamine or PCP; ICD11 6C4E.6 Psychotic disorder induced by other specified psychoactive substance).
• Recurrent depressive disorder with a history of attempted suicide (ICD11 6A71).
• Bipolar disorder (ICD11 6A60).
• Severe personality disorder judged to be contributing to impaired social function by the physician reviewing eligibility (ICD11 6D10.2).
• Disorders of Intellectual Development (defined as moderate intellectual disabilities (ICD11 6A00.1); severe intellectual disabilities (ICD11 6A00.2); profound intellectual disabilities (ICD11 6A00.3)).
• Autism Spectrum Disorders with exception of ICD11 6A02.0 Autism spectrum disorder without disorder of intellectual development and with mild or no impairment of functional language.
• Significant cognitive impairment as judged at the discretion of the physician reviewing eligibility.
• Pregnancy or absence of an acceptable method of contraception.
• Contraindications to neurosurgery (such as brain abnormalities, haemostasis disorder or contraindication to MRI) or anaesthesia.
• Severe intercurrent pathology and any other disease that could interfere with the protocol or compromise life expectancy, in the Investigator's judgement.
• Continued participation in any other interventional clinical trials.
• Any other implanted electronic devices such as implantable cardioverter defibrillators (ICD), permanent pacemakers (PPM) and drug pumps.

Sponsors & Collaborators

• University College, London: lead
• National Institute for Health Research, United Kingdom: collaborator
• University College London Hospitals: collaborator
• Northern Care Alliance NHS Foundation Trust: collaborator
• St George's University Hospitals NHS Foundation Trust: collaborator
• Royal Devon and Exeter NHS Foundation Trust: collaborator
• University of Bristol: collaborator
• University of Dundee: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• King's College London: collaborator
• University Hospital, Rouen: collaborator
• Imperial College London: collaborator

Study Sites (1)

National Hospital of Neurology & Neurosurgery

London, United Kingdom

Location

MeSH Terms

Conditions

Tourette Syndrome; Movement Disorders; Nervous System Diseases; Brain Diseases

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Central Nervous System Diseases; Tic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will have electrodes implanted in the globus pallidus interna and connected to a subcutaneous pulse generator. This will be followed by a 6 months open-phase period of stimulation for electrical parameter adjustment. Following these 6 months, participants will be randomised into two groups by the order of treatment condition (ON/OFF-stimulation vs OFF/ON-stimulation): for up to two weeks in each condition. Tic severity will be assessed and all participants will enter a 2-day interval, in the ON state, before switching to the other treatment condition for another two weeks. A mechanistic part of the study will look at possible explanations of differing responses in both the open and randomised phase. To identify the factors which predict the degree of response to DBS in TS the investigators will be looking at the role of: clinical factors: age, disease duration, tic severity at baseline, co-morbidity, Electrical parameters of stimulation, \& Imaging.

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: April 29, 2024
• Study Start: August 2, 2022
• Primary Completion: May 20, 2025
• Study Completion: June 30, 2025
• Last Updated: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)