Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome - A Pilot Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Locations
- 1
- Primary Endpoint
- Yale Global Tic Severity Scale (YGTSS)
Study Overview
Brief Summary
The motor tics associated with Tourette's syndrome may be reduced with deep brain stimulation of the anterior globus pallidus. The best area within this brain region and the best stimulation device settings are currently unknown. This is a study in which deep versus superficial electrode contact positions and two different amplitudes of stimulation are compared under scientific conditions. The hypothesis is that one contact position/stimulation amplitude combination will provide a better outcome than the others. Each study participant receives each of four different anatomical position/stimulation amplitude setting combinations over a 12 month period in randomized order followed by a 6-month period of trial-and-error device programming to optimize control of motor tics. Motor tics, potential side effects, daily functioning and quality of life are assessed at the end of each trial stimulation period. At the end of the study, the study participant continues to have long-term deep brain stimulation treatment with whatever settings provide the most relief.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 14 Years to 60 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 14 to 60 years
- •Patient Group with Tourette's syndrome - severe and resistant to medical treatment including antipsychotic medication
Exclusion Criteria
- •Surgical contraindications to deep brain stimulation surgery
- •Major Depressive Episode within the previous 6 months
- •Schizophrenia or other psychotic disorder
- •Personality disorder impairing ability to reliably comply with study protocol
- •Significant cognitive impairment
Arms & Interventions
Deep brain stimulator ventral electrode up to 2 mA
The ventral contact within the anterior globus pallidus interna near the ansa lenticularis is activated. Stimulator settings are 90 microseconds pulse width and stimulation frequency of 130 Hertz. Amplitude of stimulation is raised from zero until side effects occur or 2 mA amplitude is reached; whichever comes first.
Intervention: Deep brain stimulator ventral electrode up to 2 mA (Device)
Deep brain stimulator ventral electrode up to 3 mA
The ventral contact within the anterior globus pallidus interna near the ansa lenticularis is activated. Stimulator settings are 90 microseconds pulse width and stimulation frequency of 130 Hertz. Amplitude of stimulation is raised from zero until side effects occur or 3 mA amplitude is reached; whichever comes first.
Intervention: Deep brain stimulator ventral electrode up to 3 mA (Device)
Deep brain stimulator dorsal electrode up to 2 mA
The dorsal contact within the superior half of the anterior globus pallidus interna is activated. Stimulator settings are 90 microseconds pulse width and stimulation frequency of 130 Hertz. Amplitude of stimulation is raised from zero until side effects occur or 2 mA amplitude is reached; whichever comes first.
Intervention: Deep brain stimulator dorsal electrode up to 2 mA (Device)
Deep brain stimulator dorsal electrode up to 3 mA
The dorsal contact within the superior half of the anterior globus pallidus interna is activated. Stimulator settings are 90 microseconds pulse width and stimulation frequency of 130 Hertz. Amplitude of stimulation is raised from zero until side effects occur or 3 mA amplitude is reached; whichever comes first.
Intervention: Deep brain stimulator dorsal electrode up to 3 mA (Device)
Deep brain stimulator empirical programming
Any of the four electrode contacts on each of the two deep brain stimulation leads can be activated in any combination with any amplitude, frequency or pulse width settings to achieve optimized clinical control of motor tics whilst minimizing side effects. Both programmer and patient may be unblinded. The assessors are blinded to stimulation settings.
Intervention: Deep brain stimulator empirical programming (Device)
Outcomes
Primary Outcomes
Yale Global Tic Severity Scale (YGTSS)
Time Frame: 18 months
At the end of the 6 month non-randomized empirical stimulation period.
Yale Global Tic Severity Scale (YGTSS)
Time Frame: At baseline
Performed before surgery.
Yale Global Tic Severity Scale (YGTSS)
Time Frame: 3 months
At the end of the first of four three-month randomized blinded stimulation periods.
Yale Global Tic Severity Scale (YGTSS)
Time Frame: 6 months
At the end of the second of four three-month randomized blinded stimulation periods.
Yale Global Tic Severity Scale (YGTSS)
Time Frame: 9 months
At the end of the third of four three-month randomized blinded stimulation periods.
Yale Global Tic Severity Scale (YGTSS)
Time Frame: 12 months
At the end of the last of four three-month randomized blinded stimulation periods.
Secondary Outcomes
- Adverse effects list(12 months)
- Short Form 36(18 months)
- Modified Rush Video Rating Scale and tic counts(18 months)
- Tourette's syndrome symptom list(18 months)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(18 months)
- Montreal Cognitive Assessment (MoCA)(18 months)
- Short Form 36(At baseline)
- Modified Rush Video Rating Scale and tic counts(At baseline)
- Modified Rush Video Rating Scale and tic counts(3 months)
- Modified Rush Video Rating Scale and tic counts(6 months)
- Modified Rush Video Rating Scale and tic counts(9 months)
- Modified Rush Video Rating Scale and tic counts(12 months)
- Tourette's syndrome symptom list(At baseline)
- Tourette's syndrome symptom list(3 months)
- Tourette's syndrome symptom list(6 months)
- Tourette's syndrome symptom list(9 months)
- Tourette's syndrome symptom list(12 months)
- Short Form 36(3 months)
- Short Form 36(6 months)
- Short Form 36(9 months)
- Short Form 36(12 months)
- Montreal Cognitive Assessment (MoCA)(At baseline)
- Montreal Cognitive Assessment (MoCA)(3 months)
- Montreal Cognitive Assessment (MoCA)(6 months)
- Montreal Cognitive Assessment (MoCA)(9 months)
- Montreal Cognitive Assessment (MoCA)(12 months)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(At baseline)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(3 months)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(6 months)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(9 months)
- Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS)(12 months)
- Adverse effects list(3 months)
- Adverse effects list(6 months)
- Adverse effects list(9 months)
Investigators
Professor Christopher Lind
Consultant Neurosurgeon
The University of Western Australia