Clinical trial NCT06388291: Deep Brain Stimulation in Tourette Syndrome
Official title: Double Blind Comparison of Optimised Deep Brain Stimulation for Severe Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tourette Syndrome
Deep Brain Stimulation
Keywords: Movement Disorders
Nervous System Diseases
Brain Diseases
Functional Disorder
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: University College London Hospitals
name: Northern Care Alliance NHS Foundation Trust
name: St George's University Hospitals NHS Foundation Trust
name: Royal Devon and Exeter NHS Foundation Trust
name: University of Bristol
name: University of Dundee
name: London School of Hygiene and Tropical Medicine
name: King's College London
name: University Hospital, Rouen
name: Imperial College London
First posted: 2024-04-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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): one group will be kept with the stimulation on ("ON-stimulation") and the other switched off ("OFF-stimulation") for up to two weeks. 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.
Primary purpose: TREATMENT

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

Detailed description: Tourette syndrome (TS) is a neuropsychiatric disorder with patients exhibiting multiple motor tics and at least one vocal tic. When these tics are distressing, medications or behavioural therapy can be used to control symptoms.

However, there are a small number of patients with very severe tics who are unresponsive to these conventional treatments and suffer a major negative impact on their quality of life. This limits their social interaction and access to most jobs. These patients are in urgent need of more effective treatments.

Deep brain stimulation (DBS) is a technique that involves the surgical implantation of two thin wires (electrodes) in the right and left globus pallidus, areas of the brain responsible for the control of body movement. The electrodes are connected to a stimulator placed on the chest under the skin that sends electrical signals to the brain. This type of surgery is routinely used for disorders such as Parkinson's disease and has also been used in a smaller number of TS patients.

DBS is an accepted treatment for conditions such as Parkinson's disease, dystonia and tremor. In experienced teams the risks associated with the surgery and the device are very low. A small number of patients with Tourette syndrome around the world have benefited from DBS; nevertheless, more evidence is needed before DBS can be made available as an NHS treatment for severely affected patients and NHS England has prioritised this research topic.

Eligibility criteria: Inclusion Criteria:

Adult patients aged 18 and over:

1. with chronic, severe, treatment refractory Tourette Syndrome, as defined by a Yale Global Tic Severity Scale score (YGTSS (global)) \>50/100
2. 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
3. who have provided agreement to participate and written informed consent

Exclusion Criteria:

1. Schizophrenia or other primary psychotic disorder (schizophrenia (ICD11 6A20); delusional disorders (ICD11 6A24); schizoaffective disorder (ICD11 6A21).
2. 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).
3. Recurrent depressive disorder with a history of attempted suicide (ICD11 6A71).
4. Bipolar disorder (ICD11 6A60).
5. Severe personality disorder judged to be contributing to impaired social function by the physician reviewing eligibility (ICD11 6D10.2).
6. Disorders of Intellectual Development (defined as moderate intellectual disabilities (ICD11 6A00.1); severe intellectual disabilities (ICD11 6A00.2); profound intellectual disabilities (ICD11 6A00.3)).
7. 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.
8. Significant cognitive impairment as judged at the discretion of the physician reviewing eligibility.
9. Pregnancy or absence of an acceptable method of contraception.
10. Contraindications to neurosurgery (such as brain abnormalities, haemostasis disorder or contraindication to MRI) or anaesthesia.
11. Severe intercurrent pathology and any other disease that could interfere with the protocol or compromise life expectancy, in the Investigator's judgement.
12. Continued participation in any other interventional clinical trials.
13. Any other implanted electronic devices such as implantable cardioverter defibrillators (ICD), permanent pacemakers (PPM) and drug pumps.

Primary outcomes:
measure: 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
timeFrame: 4 weeks
Secondary outcomes:
measure: MRVRS at the end of the OFF-stimulation state versus the end of the ON-stimulation state in the blinded, randomised crossover phase.
timeFrame: 4 weeks
measure: Change in the MRVRS between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the YGTSS (global) between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the GTS-QOL questionnaire measures at baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the YBOCS between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the BDI scale between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the BAI scale between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Change in the BAARS-IV between baseline 0 and the end of the open-phase (Baseline 1)
timeFrame: 24 weeks
measure: Safety of DBS as indicated by the number of participants with any adverse events and number with any serious adverse events
timeFrame: 28 weeks
Other outcomes:
measure: A mechanistic part of the study will look at possible explanations of differing responses in both the open and randomised phase.
timeFrame: 28 weeks
Locations:
city: London
country: United Kingdom
facility: National Hospital of Neurology & Neurosurgery
Study officials:
References: