Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by The University of Western Australia
Sponsor:
Collaborators:
Sir Charles Gairdner Hospital
Australian Neuromuscular Research Institute
Information provided by (Responsible Party):
Professor Christopher Lind, The University of Western Australia
ClinicalTrials.gov Identifier:
NCT02112253
First received: March 22, 2014
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Tourette's Syndrome
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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimising Anterior Pallidal Deep Brain Stimulation for Tourette's Syndrome - A Pilot Study

Resource links provided by NLM:


Further study details as provided by The University of Western Australia:

Primary Outcome Measures:
  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed before surgery.

  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    At the end of the first of four three-month randomized blinded stimulation periods.

  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    At the end of the second of four three-month randomized blinded stimulation periods.

  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the last of four three-month randomized blinded stimulation periods.

  • Yale Global Tic Severity Scale (YGTSS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.


Secondary Outcome Measures:
  • Modified Rush Video Rating Scale and tic counts [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed before surgery.

  • Modified Rush Video Rating Scale and tic counts [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    At the end of the first of four three-month randomized blinded stimulation periods.

  • Modified Rush Video Rating Scale and tic counts [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    At the end of the second of four three-month randomized blinded stimulation periods.

  • Modified Rush Video Rating Scale and tic counts [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Modified Rush Video Rating Scale and tic counts [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the last of four three-month randomized blinded stimulation periods.

  • Modified Rush Video Rating Scale and tic counts [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.

  • Tourette's syndrome symptom list [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed before surgery.

  • Tourette's syndrome symptom list [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    At the end of the first of four three-month randomized blinded stimulation periods.

  • Tourette's syndrome symptom list [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    At the end of the second of four three-month randomized blinded stimulation periods.

  • Tourette's syndrome symptom list [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Tourette's syndrome symptom list [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Tourette's syndrome symptom list [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.

  • Short Form 36 [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Quality of life outcome measure. Performed before surgery.

  • Short Form 36 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Quality of life outcome measure. At the end of the first of four three-month randomized blinded stimulation periods.

  • Short Form 36 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Quality of life outcome measure. At the end of the second of four three-month randomized blinded stimulation periods.

  • Short Form 36 [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Quality of life outcome measure. At the end of the third of four three-month randomized blinded stimulation periods.

  • Short Form 36 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Quality of life outcome measure. At the end of the last of four three-month randomized blinded stimulation periods.

  • Short Form 36 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed before surgery.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    At the end of the first of four three-month randomized blinded stimulation periods.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    At the end of the second of four three-month randomized blinded stimulation periods.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the last of four three-month randomized blinded stimulation periods.

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed before surgery.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    At the end of the first of four three-month randomized blinded stimulation periods.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    At the end of the second of four three-month randomized blinded stimulation periods.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    At the end of the third of four three-month randomized blinded stimulation periods.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    At the end of the last of four three-month randomized blinded stimulation periods.

  • Psychiatric interview including: Mini International Neuropsychiatric Interview (MINI; version 5.0.0), Montgomery Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    At the end of the 6 month non-randomized empirical stimulation period.

  • Adverse effects list [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Adverse effects list [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Adverse effects list [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    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.

  • Adverse effects list [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Adverse effects list [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Registered and notified to principal investigator whenever detected. Also specifically sought at the end of the 6 month non-randomized empirical stimulation period.


Estimated Enrollment: 10
Study Start Date: March 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   14 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02112253

Contacts
Contact: Christopher Lind, FRACS +61 8 9346 2865 Christopher.Lind@health.wa.gov.au
Contact: Megan Thorburn, CNC Megan.Thorburn@health.wa.gov.au

Locations
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Perth, Western Australia, Australia, 6009
Contact: Christopher Lind, MBChB, FRACS    +61-8-9346-2865    Christopher.Lind@health.wa.gov.au   
Contact: Megan Thorburn, RN    +61-8-9346-3333    Megan.Thorburn@health.wa.gov.au   
Principal Investigator: Christopher Lind, MBChB, FRACS         
Sponsors and Collaborators
The University of Western Australia
Sir Charles Gairdner Hospital
Australian Neuromuscular Research Institute
Investigators
Principal Investigator: Christopher Lind, FRACS The University of Western Australia
  More Information

Additional Information:
No publications provided

Responsible Party: Professor Christopher Lind, Consultant Neurosurgeon, The University of Western Australia
ClinicalTrials.gov Identifier: NCT02112253     History of Changes
Other Study ID Numbers: 2012-120
Study First Received: March 22, 2014
Last Updated: April 9, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee

Keywords provided by The University of Western Australia:
Tourette's syndrome
Deep brain stimulation
Stereotactic surgery
Globus pallidus interna
Tics

Additional relevant MeSH terms:
Syndrome
Tourette Syndrome
Disease
Pathologic Processes
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tic Disorders
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mental Disorders Diagnosed in Childhood
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014