Tourette Syndrome Deep Brain Stimulation
The Human Thalamocortical Network in Tourette Syndrome
4 other identifiers
interventional
10
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Mar 2014
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 3, 2014
CompletedFirst Posted
Study publicly available on registry
February 6, 2014
CompletedStudy Start
First participant enrolled
March 20, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 25, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 24, 2023
CompletedResults Posted
Study results publicly available
September 5, 2024
CompletedSeptember 5, 2024
August 1, 2024
7.4 years
February 3, 2014
October 18, 2023
August 30, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With a 40% Reduction in Total Tics on the Yale Global Tic Severity Scale (YGTSS) With CDBS (Period 1)
The Yale Global Tic Severity Scale (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. The total scale has been used in this study and has a range of 0-50. A higher score indicates a higher severity of symptoms. Patients reach the outcome measure with a 40% reduction of YGTSS at month 6 post-op compared to baseline (i.e., 40% improvement in their tic severity scale).
Baseline to 6 months post-surgery
Study Arms (2)
Continuous Deep Brain Stimulation (DBS)
EXPERIMENTALSubjects' 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.
Responsive Brain Stimulation (RBS Setting)
EXPERIMENTALEligible participants from Arm 1 will be switch to the RBS intervention.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- Must be 21+ 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)
You may not qualify if:
- 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)
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Floridalead
- Medtroniccollaborator
- National Institute of Neurological Disorders and Stroke (NINDS)collaborator
Study Sites (1)
University of Florida
Gainesville, Florida, 32607, United States
Related Publications (1)
Cagle JN, Okun MS, Cernera S, Eisinger RS, Opri E, Bowers D, Ward H, Foote KD, Gunduz A. Embedded Human Closed-Loop Deep Brain Stimulation for Tourette Syndrome: A Nonrandomized Controlled Trial. JAMA Neurol. 2022 Oct 1;79(10):1064-1068. doi: 10.1001/jamaneurol.2022.2741.
PMID: 36094652DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Michael Okun
- Organization
- Univeristy of Florida
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Okun, MD
University of Florida
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 3, 2014
First Posted
February 6, 2014
Study Start
March 20, 2014
Primary Completion
August 25, 2021
Study Completion
August 24, 2023
Last Updated
September 5, 2024
Results First Posted
September 5, 2024
Record last verified: 2024-08