Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome - A Pilot Study

Conditions
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Tourette's Syndrome

Intervention / Treatment
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* Device: Deep brain stimulator ventral electrode up to 2 mA
* Device: Deep brain stimulator ventral electrode up to 3 mA
* Device: Deep brain stimulator dorsal electrode up to 2 mA
* Device: Deep brain stimulator dorsal electrode up to 3 mA
* Device: Deep brain stimulator empirical programming


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep brain stimulator ventral electrode up to 2 mA<br>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. | Device: Deep brain stimulator ventral electrode up to 2 mA<br> <br> |
| Experimental: Deep brain stimulator ventral electrode up to 3 mA<br>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. | Device: Deep brain stimulator ventral electrode up to 3 mA<br> <br> |
| Experimental: Deep brain stimulator dorsal electrode up to 2 mA<br>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. | Device: Deep brain stimulator dorsal electrode up to 2 mA<br> <br> |
| Experimental: Deep brain stimulator dorsal electrode up to 3 mA<br>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. | Device: Deep brain stimulator dorsal electrode up to 3 mA<br> <br> |
| Active Comparator: Deep brain stimulator empirical programming<br>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. | Device: Deep brain stimulator empirical programming<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yale Global Tic Severity Scale (YGTSS) | Performed before surgery. | At baseline | 
| Yale Global Tic Severity Scale (YGTSS) | At the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Yale Global Tic Severity Scale (YGTSS) | At the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Yale Global Tic Severity Scale (YGTSS) | At the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Yale Global Tic Severity Scale (YGTSS) | At the end of the last of four three-month randomized blinded stimulation periods. | 12 months | 
| Yale Global Tic Severity Scale (YGTSS) | At the end of the 6 month non-randomized empirical stimulation period. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rush Video Rating Scale and tic counts | Performed before surgery. | At baseline | 
| Modified Rush Video Rating Scale and tic counts | At the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Modified Rush Video Rating Scale and tic counts | At the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Modified Rush Video Rating Scale and tic counts | At the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Modified Rush Video Rating Scale and tic counts | At the end of the last of four three-month randomized blinded stimulation periods. | 12 months | 
| Modified Rush Video Rating Scale and tic counts | At the end of the 6 month non-randomized empirical stimulation period. | 18 months | 
| Tourette's syndrome symptom list | Performed before surgery. | At baseline | 
| Tourette's syndrome symptom list | At the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Tourette's syndrome symptom list | At the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Tourette's syndrome symptom list | At the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Tourette's syndrome symptom list | At the end of the third of four three-month randomized blinded stimulation periods. | 12 months | 
| Tourette's syndrome symptom list | At the end of the 6 month non-randomized empirical stimulation period. | 18 months | 
| Short Form 36 | Quality of life outcome measure. Performed before surgery. | At baseline | 
| Short Form 36 | Quality of life outcome measure. At the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Short Form 36 | Quality of life outcome measure. At the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Short Form 36 | Quality of life outcome measure. At the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Short Form 36 | Quality of life outcome measure. At the end of the last of four three-month randomized blinded stimulation periods. | 12 months | 
| Short Form 36 | At the end of the 6 month non-randomized empirical stimulation period. | 18 months | 
| Montreal Cognitive Assessment (MoCA) | Performed before surgery. | At baseline | 
| Montreal Cognitive Assessment (MoCA) | At the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Montreal Cognitive Assessment (MoCA) | At the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Montreal Cognitive Assessment (MoCA) | At the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Montreal Cognitive Assessment (MoCA) | At the end of the last of four three-month randomized blinded stimulation periods. | 12 months | 
| Montreal Cognitive Assessment (MoCA) | At the end of the 6 month non-randomized empirical stimulation period. | 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) | Performed before surgery. | 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) | At the end of the first of four three-month randomized blinded stimulation periods. | 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) | At the end of the second of four three-month randomized blinded stimulation periods. | 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) | At the end of the third of four three-month randomized blinded stimulation periods. | 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) | At the end of the last of four three-month randomized blinded stimulation periods. | 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 the end of the 6 month non-randomized empirical stimulation period. | 18 months | 
| Adverse effects list | Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the first of four three-month randomized blinded stimulation periods. | 3 months | 
| Adverse effects list | Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the second of four three-month randomized blinded stimulation periods. | 6 months | 
| Adverse effects list | Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the third of four three-month randomized blinded stimulation periods. | 9 months | 
| Adverse effects list | Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the last of four three-month randomized blinded stimulation periods. | 12 months | 
| Adverse effects list | Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the 6 month non-randomized empirical stimulation period. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tourette's syndrome, Deep brain stimulation, Stereotactic surgery, Globus pallidus interna, Tics