Tourette Syndrome Deep Brain Stimulation

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by University of Florida
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT02056873
First received: February 3, 2014
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the effectiveness and safety of deep brain stimulation (DBS) as a possible new treatment for Tourette Syndrome (TS).

This investigation will (1) test the hypothesis that centromedian (CM) continuous brain stimulation will be an effective, safe method for the treatment of tics in medication refractory TS, (2) will define the intra-operative and post-operative physiological changes, and (3) will test the hypothesis that responsive brain stimulation (RBS) will provide an alternative to chronic DBS in TS.


Condition Intervention
Tourette Syndrome
Device: DBS System
Device: DBS System (RBS Setting)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tourette Syndrome Deep Brain Stimulation: Modulation of Oscillations for the Treatment of Tourette Syndrome

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Reduction in total tics on the Yale Global Tic Severity Scale (YGTSS) after 6 months as an effect of centromedian (CM) continuous DBS stimulation [ Time Frame: Baseline to 6 months post-surgery ] [ Designated as safety issue: No ]
    The YGTSS is a 10-item semi-structured clinician-rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The items pertaining to the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. A higher score indicates a higher severity of symptoms.

  • Correlation between increase in gamma oscillations and improvement in TS symptomatology [ Time Frame: Date of surgery until 24 months post-surgery ] [ Designated as safety issue: No ]
    The investigators will collect real time, local field potentials (LFP) that are time synchronized with clinical behavior, from the CM region, pre-motor, and motor cortex in order to study the thalamocortical interactions and determine if there is a correlation between increases in gamma oscillations and improvement in Tourette Syndrome (TS) symptomology.

  • Responsive brain stimulation (RBS) as an effective alternative to continuous DBS stimulation [ Time Frame: Baseline until 24 months post-surgery ] [ Designated as safety issue: No ]

    Scores on the YGTSS during continuous stimulation will be compared to scores on the YGTSS during RBS.

    The YGTSS is a 10-item semi-structured clinician-rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The items pertaining to the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. A higher score indicates a higher severity of symptoms.


  • Reduction in total tics on the YGTSS after 24 months as an effect of centromedian (CM) continuous DBS stimulation [ Time Frame: Baseline to 24 months post-surgery ] [ Designated as safety issue: No ]
    The YGTSS is a 10-item semi-structured clinician-rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The items pertaining to the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. A higher score indicates a higher severity of symptoms.


Estimated Enrollment: 10
Study Start Date: May 2014
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deep Brain Stimulation (DBS)

Subjects' DBS surgical intervention requires implantation of a DBS system: two CM thalamic leads (one in each brain hemisphere), two ECOG strip leads (one in each brain hemisphere), and two neurostimulators implanted in the chest.

The ECOG strip lead is implanted into the brain to provide an interface through which stimulation can be delivered or activity of the brain can be monitored by the device, or observed by a clinician using a programmer.

Neurostimulator and leads system includes a programmer, which includes a wand and telemetry interface, and a patient remote control to check battery status and whether the device is on or off. The programmer is used to set up the device, including setup of stimulation and recording, as well as to retrieve data for subsequent review.

Device: DBS System

The DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips.

The DBS system will be set to provide continuous stimulation for the 6 months following surgery. Subjects will be seen monthly for evaluation as a part of normal clinical care for DBS. At 6 months, the investigators will determine whether or not the subject is a candidate for responsive brain stimulation (RBS). Qualifying subjects will have the option to have their settings changed in order to participate in the RBS stimulation intervention. Subjects who do not qualify or do not participate will continue to receive this intervention for the duration of the study. These subjects will been seen every 6 months for evaluation as part of normal clinical care for DBS.

Other Names:
  • Neurostimulator: Medtronic Activa PC+S Device Model 37604
  • CM thalamic leads: Medtronic Leads Model 3387
  • ECOG strip leads: The Resume II Medtronic Model 3587A
Device: DBS System (RBS Setting)

The DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips.

Six months post-surgery, the DBS system will be set to provide responsive stimulation for the duration of the study. Subjects will be seen every 6 months for evaluation as a part of normal clinical care for DBS.

Data gathered from the subject during the first 6 months will be used to determine if this intervention is applicable for each individual subject. Subjects who do not qualify will continue to receive the other study intervention.

Other Names:
  • Neurostimulator: Medtronic Activa PC+S Device Model 37604
  • CM thalamic leads: Medtronic Leads Model 3387
  • ECOG strip leads: The Resume II Medtronic Model 3587A

Detailed Description:

Normal clinical care for TS includes cognitive behavior therapy, medication, supportive psychotherapy, and/or a combination of the two. To meet entry criteria for this study, you must have already tried these methods and they did not help your symptoms. DBS is considered experimental for the treatment of TS and would not be done as normal clinical care.

Participation in this study will require extensive pre-surgical screening to determine eligibility for DBS surgery, a DBS surgical procedure, and regular follow-ups. Subjects will be seen monthly post surgery for 6 months. After 6 months, data will be assessed and RBS may be offered as a stimulation setting. If so, the stimulator settings will be changed from chronic to responsive. If not, the subject will continue to receive chronic DBS stimulation. Subsequent visits will be scheduled every 6 months until a total of 24 months of study participation.

At the end of the initial 24-month study period, subjects will have the choice of 1) continuing active stimulation at the current setting, 2) continuing stimulation but searching for a new setting, 3) discontinuing stimulation (turning the device off), 4) having the device removed. If the subject continues to receive active stimulation, they will be followed by the PI and seen at yearly intervals until the DBS system is commercially available, FDA approved for the treatment of TS, or unavailable for patient use.

  Eligibility

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be 22+ years of age
  • Diagnosis of Tourette Syndrome (TS) in accordance to the Diagnostic and Statistical Manual of Mental DIsorders (DSM-V) criteria
  • Yale Global Tic Severity Scale (YGTSS) must be ≥35/50 for at least 12 months; Motor Tic subscore must be ≥15
  • TS must be causing incapacitation with severe distress, self-injurious behavior, and/or quality of life disruption
  • TS must be medication refractory. Criteria to determine if medication refractory is the exact criteria stated by Mink et. al TSA DBS Guidelines published in 2006: Subjects must have been treated by a psychiatrist or neurologist experienced in TS with therapeutic doses of either 1-4 mg/day of haloperidol or 2-8 mg/day of pimozide, risperidone (1-3 mg/day), and aripiprazole (2.5-5 mg/day). Must be at minimum a single trial with an alpha-2 adrenergic agonist (0.1-0.3 mg/day)
  • Clinically relevant depression must be pharmacologically treated and deemed stable
  • Must have been stabilized for 1 month on TS medication without a dose change prior to surgical intervention. If medication trials resulted in discontinuation of TS medications, the subject must be stabilized for 3 months off TS medicines
  • Must be willing to keep TS related medications stable and unchanged throughout the trial
  • Must have been offered habit reversal therapy/cognitive behavioral intervention therapy (HRT) if subject did not have it prior to enrollment. (Subjects not required to participate in HRT but it will be highly encouraged, and must be completed prior to start of this study's protocol. Those who improve significantly will be excluded from receiving DBS surgery)
  • If tic is focal or addressable by botulinum toxin treatment, the study neurologist will offer to administer a trial of botulinum toxin prior to consideration of surgical therapy. (If the subject chooses not to have the treatment, they cannot participate in the study. If the patient responds satisfactorily and their quality of life significantly improves, they will be excluded)

Exclusion Criteria:

  • Any previous neurological intervention including DBS or ablative brain lesions, any metal in the head, and any type of implanted stimulator
  • Untreated or unstable anxiety, depression, bipolar disorder, or other Axis I psychiatric disorder
  • Presence of psychotic features
  • Significant psychosocial factors that can cause increased risk
  • The presence of only simple motor tics, a movement disorder other than TS, or medication related movement disorders from TS medications
  • Severe medical co-morbidity 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
  • Abnormal brain magnetic resonance imaging (MRI) scan, including severe atrophy, hydrocephalus, stroke, structural lesions, demyelinating lesions, or infectious lesions that would potentially confound the outcome or safety of the surgery as judged by the study neurosurgeon
  • Dementia or cognitive dysfunction that will place the subject at risk for worsening cognition, and/or may impact the ability to cooperate with tasks involved in the study
  • Any attempt or intent of suicide in the last 6 months
  • Significant substance abuse or dependence within the last 6 months
  • Multiple failed medication treatments of inadequate dose or duration
  • History of noncompliance with previous medical and psychosocial treatment efforts
  • Severe head banging tics
  • Women of child-bearing potential who are pregnant or planning pregnancy (urine pregnancy test required)
  • Positive urine drug screen for illicit substances (urine drug screen required)
  • History of multiple surgical procedures with poor outcomes
  • Unexplained gaps in medical history
  • Pending lawsuits or other legal action
  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: NCT02056873

Contacts
Contact: Stacy Merritt, MA 352-273-5614 stacy.merritt@neurology.ufl.edu
Contact: Erin Monari, Ph.D 352-294-5030 erin.hastings@neurology.ufl.edu

Locations
United States, Florida
University of Florida Not yet recruiting
Gainesville, Florida, United States, 32607
Principal Investigator: Michael Okun, MD         
Sub-Investigator: Kelly Foote, MD         
Sub-Investigator: Dawn Bowers, PhD         
Sponsors and Collaborators
University of Florida
Medtronic
Investigators
Principal Investigator: Michael Okun, MD University of Florida
  More Information

Additional Information:
No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02056873     History of Changes
Other Study ID Numbers: 850-2013
Study First Received: February 3, 2014
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board

Keywords provided by University of Florida:
deep brain stimulation
DBS
tourette
tourette's
tourette syndrome
TS

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 July 23, 2014