A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome

A Randomised, Controlled, Crossover Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Severe Tourette Syndrome

The purpose of this study is to investigate whether deep brain stimulation (DBS) of the globus pallidus internum (GPi) can alleviate tics in Gilles de la Tourette syndrome (GTS) and whether this treatment has any influence on social, psychological and behavioral disability and quality of life.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome
• Intervention / Treatment: Procedure: Bilateral GPi Deep Brain Stimulation

Detailed Description

This study is aimed at adults who have severe Tourette syndrome and who have found that conventional treatments, such as drugs, do not control their symptoms sufficiently or cannot be tolerated.

The first two clinic visits will involve assessments. Participants will fill in a number of questionnaires and be examined by a psychiatrist and a neurologist. At the second visit, the patient will provide consent for participation and will undergo formal tests to find out if the participant is suitable and willing to undergo the research study and to record the type and severity of their Tourette syndrome symptoms.

The third visit will be an admission to hospital to have the deep brain stimulation (DBS) devices implanted. The admission to hospital should be around five days in duration.

At the first post operative follow-up visit, the patient will be placed into a "stimulator on" group or a "stimulator off" group. To try and make sure that these groups are the same to start with, each patient is put into a group by chance (randomly). This visit will take place around six weeks after surgery. In this trial, the participant will have an equal chance of being in the "on" or the "off" group first. This trial is also a "blinded" trial, neither the patient nor the researchers performing the assessments will know which group the patient is in.

At the next visit, 3 months later, the patient will have a further assessment. If their stimulators have been "on" for the first 3 months, they will be switched off. If they have been "off" they will be switched on.

At the next visit, 3 months later, the patient will be assessed again and then given the opportunity to carry on the trial with the stimulators switched on for long term follow up.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • UCL Institute of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The participant must be adult with stable Tourette syndrome.
2. The participant must have a chronic and severe tic disorder with severe functional impairment, with a Yale Tourette Severity Scale score of at least 35/55 for at least 12 months prior to surgery.
3. The participant must have failed conventional medical treatment at therapeutic doses of three classes of medication.
4. The participant must not be suitable for behavioural intervention or that this intervention is inappropriate or unsuccessful.
5. The participant must have been on stable and optimised treatment of co-morbid conditions for at least 6 months.
6. The participant must be actively involved with and compliant with any psychosocial interventions.
7. The patient must be compliant with treatment plans.

Exclusion Criteria:

1. The tic disorder is attributable to any other condition.
2. Any other medical or psychiatric disorders that substantially increase the risk of a failed procedure or that would significantly impede recovery.
3. Psychosocial factors which might impede operative and post-operative care and research participation.
4. Coagulation problems
5. Other disease compromising life expectancy
6. Patient likely to benefit from psychological intervention
7. Patient unwilling to co-operate with post operative assessment and care
8. Pregnancy.
9. Participant under 20 years old.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DBS Off first	Procedure: Bilateral GPi Deep Brain Stimulation; Bilateral GPi Deep Brain Stimulation
Experimental: DBS On First	Procedure: Bilateral GPi Deep Brain Stimulation; Bilateral GPi Deep Brain Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Yale Global Tic Severity Scale	The Change in Scores on the Yale Global Tic Severity Scale will be compared between defined periods with stimulation switched ON v stimulation switched OFF.	Three months after stimulation switched ON v three months after stimulation switched OFF

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Modified Rush Video Rating scale	Three months after stimulation switched ON v three months after stimulation switched OFF
Change in Yale Brown Obsessive Compulsive Scale	Three months after stimulation switched ON v three months after stimulation switched OFF
Change in Neuropsychiatric Inventory	Three months after stimulation switched ON v three months after stimulation switched OFF
Change in Tourette Quality of life scale	Three months after stimulation switched ON v three months after stimulation switched OFF
Change in MOVES scale	Three months after stimulation switched ON v three months after stimulation switched OFF
Change in Beck Depression Inventory	Three months after stimulation switched ON v three months after stimulation switched OFF

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Thomas Foltynie, MBBS PhD, UCL Institute of Neurology

Publications and helpful links

General Publications

• Kefalopoulou Z, Zrinzo L, Jahanshahi M, Candelario J, Milabo C, Beigi M, Akram H, Hyam J, Clayton J, Kass-Iliyya L, Silverdale M, Evans J, Limousin P, Hariz M, Joyce E, Foltynie T. Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial. Lancet Neurol. 2015 Jun;14(6):595-605. doi: 10.1016/S1474-4422(15)00008-3. Epub 2015 Apr 14.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 16, 2012
• First Submitted That Met QC Criteria: July 20, 2012
• First Posted (Estimate): July 23, 2012

Study Record Updates

• Last Update Posted (Estimate): March 19, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: UCL 11/0226