Brain Stimulation for the Treatment of Tourette Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01329198
First received: March 25, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this trial is to determine whether a particular type of Deep Brain Stimulation (DBS), scheduled Deep Brain stimulation (SBS), is an effective and safe treatment for Tourettte syndrome (TS).

The trial will also examine the brain activity associated with TS and tics and explore the possibility of responsive brain stimulation (RBS).


Condition Intervention
Tourette Syndrome
Device: NeuroPace RNS® System Deep Brain Stimulator

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Scheduled and Responsive Brain Stimulation for the Treatment of Tourette Syndrome

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Change in Yale Global Tic Severity Scale (YGTSS) Total Score From Baseline to 6 Months [ Time Frame: Baseline to 6 Months ] [ Designated as safety issue: No ]

    The YGTSS is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are:

    • Total Motor Tic Score (0-25)
    • Total Phonic Tic Score (0-25
    • Total Tic Score (0-50)
    • Overall Impairment Rating (0-50)
    • Global Severity Score (0-7)

    The YGTSS Total Score is obtained by adding the Total Tic Score to the Overall Impairment Rating. The efficacy of the intervention will be assessed by comparing each subject's 6-month YGTSS Total Score to the pre-operative value for the same patient. Efficacy is considered 50% or greater reduction in this score.



Secondary Outcome Measures:
  • Correlation of Tics and Neural Physiology [ Time Frame: Baseline to 6 Months ] [ Designated as safety issue: No ]
    Electrical recordings of electroencephalography activity were taken from each subject's implanted leads at each visit from baseline to 6 months. At baseline, the recordings were taken with the device in the off state (not stimulating), while at the 6 month visits the recordings were taken with the subject's device set to optimal parameters for tic control. Using Pearson's correlation coefficient, the variations in frequency and power which were observed were correlated with the Yale Gordon Tic Severity (YGTSS) scores obtained during primary outcome testing.


Enrollment: 5
Study Start Date: September 2009
Estimated Study Completion Date: November 2017
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Sham DBS
Sham stimulation in which no electrical charge is delivered through the Neuropace RNS system.
Device: NeuroPace RNS® System Deep Brain Stimulator
  • There will be a one month post-operative period during which stimulation is not turned on.
  • One month post-implant, subjects will be randomized one to one in a blinded fashion to receive active or sham stimulation.
  • By Day 60, all subjects will be programmed to receive active stimulation. Physiological data will be collected for Specific Aim 2 of the study.
  • Both the sham and the active groups (3 subjects in each group) will undergo identical programming procedures at 30 and 60 days.
Other Name: NeuroPace DBS
Active Comparator: Active DBS
Active stimulation through the Neuropace RNS system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects
Device: NeuroPace RNS® System Deep Brain Stimulator
  • There will be a one month post-operative period during which stimulation is not turned on.
  • One month post-implant, subjects will be randomized one to one in a blinded fashion to receive active or sham stimulation.
  • By Day 60, all subjects will be programmed to receive active stimulation. Physiological data will be collected for Specific Aim 2 of the study.
  • Both the sham and the active groups (3 subjects in each group) will undergo identical programming procedures at 30 and 60 days.
Other Name: NeuroPace DBS

Detailed Description:

DBS is a surgical procedure that seeks to change the brain's electrical signalling by means of applied electrical current. To this end, a wire with tiny stimulating electrodes is implanted into one or both sides of the brain. An electrode is a small piece of metal used to take an electric current to or from a power source. These electrodes are connected under the skin on the scalp to a small electrical unit called an INS (implantable neurostimulator), which is similar to a heart pacemaker. The device sends out electrical impulses that appear to change the normal flow of electricity in the brain.

The wires which house the electrodes will be implanted on both sides of the brain oriented towards the centromedian thalamus-parafascicular complex. This region of the brain has to date the greats number of documented cases revealing significant improvements in motor tics.

This region of the brain will also provide a target where physiological changes related to motor tics are likely to be discovered.

The device we propose for this study has several features that make it more suitable for use in the TS population than other devices. It is self-contained in the skull and brain, and contains no tunneled neck connector wire and no chest pacemaker deice. This will help to lessen infection, and will assist in limiting device-related fractures due to tics involving neck region. Also, the system can record electro-encephalograph data from the area of the electrodes, which will assist us in gathering information about what specific physiological changes are correlated with tics.

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of TS must be made by both a neurologist and a psychiatrist and must meet standardized criteria
  • must have a minimum score on the primary tic rating scale
  • symptoms must be causing significant impairment in functioning, making it impossible or almost impossible to do daily activities, including work or school and interactions with friends and family, causing severe distress and a poor quality of life
  • symptoms have not responded well enough to medications prescribed by a neurologist or psychiatrist experienced in treating TS. Must have had trials of drugs from three different classes of drugs that have not worked.
  • must have received stable and effective treatment of any other existing medical or psychological problems for the past 6 months.
  • current TS related-medication(s) must be stable for at least a month without a dose change prior to surgery and must be willing to keep these medications stable and unchanged throughout the study or must be off of TS-related medications for at least three months prior to surgery
  • If tics involve only one group of muscles or might be controllable by botulinum toxin treatment, must try botulinum treatment before considering surgery.
  • must have a negative urine drug screen
  • must give informed consent

Exclusion Criteria:

  • have a simple motor tic or movement disorder other than TS, or medication-related movement disorders from TS medications
  • have had any previous brain surgery including deep brain stimulation, ablative capsulotomy or cingulotomy
  • have another psychiatric condition (including body dysmorphic disorder, a delusional disorder or a biological brain disorder), dementia or cognitive dysfunction that would place subject at risk for worsening cognition and/or may impact ability to comply with study procedures. Also included is any other psychiatric disorder that requires medications or treatments that would interfere with the functioning of the DBS device.
  • have any significant substance abuse or dependence (e.g., stimulants, alcohol, opiates, benzodiazepines) within the past six months
  • have a severe medical disease including cardiovascular disorder, lung disorder, kidney disease, chronic neurological disease, hematological disease, or frailty that impacts tolerability of the surgery as judged by the screening physicians
  • pre-surgery MRI is considered abnormal. You may also be excluded if your brain is considered very small.
  • have a history of serious suicidal behavior, are unable to control suicide attempts, or are currently at risk of suicide, in the judgement of the investigator
  • have head-banging tics or tics that have the potential to damage the RNS System
  • are currently pregnant or breast-feeding, plan to become pregnant during the study, or are not using effective contraception
  • are currently enrolled in another investigational study
  • have an implant such as a pacemaker or neurostimulator containing electrical circuitry or that generates electrical signals
  • have any metal orthopedic pins or plates, metal orthodontics, or non-removable body jewelry
  • require diathermy treatments during physical or occupational therapy
  • have a problem that will require repeat Magnetic Resonance Imaging (MRI) scans
  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: NCT01329198

Locations
United States, Florida
University of Florida Movement Disorders Center
Gainesville, Florida, United States, 32611
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Michael Okun, MD University of Florida
  More Information

No publications provided by University of Florida

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01329198     History of Changes
Other Study ID Numbers: 00068500
Study First Received: March 25, 2011
Results First Received: April 8, 2014
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
tourette
tourette's
TS
tourette syndrome
tourette's syndrome

Additional relevant MeSH terms:
Tourette Syndrome
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 August 18, 2014