Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome

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

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 Overview

• Status: Withdrawn
• Conditions: Tourette's Syndrome
• Intervention / Treatment: 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

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Western Australia
• Collaborators: Sir Charles Gairdner Hospital; Perron Institute for Neurological and Translational Science
• Investigators: Principal Investigator: Christopher Lind, FRACS, The University of Western Australia

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 14, 2021
• Study Completion (Anticipated): May 14, 2021

Study Registration Dates

• First Submitted: March 22, 2014
• First Submitted That Met QC Criteria: April 9, 2014
• First Posted (Estimate): April 11, 2014

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Stereotactic surgery; Deep brain stimulation; Tourette's syndrome; Tics; Globus pallidus interna
• 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: 2012-120