Clinical trial NCT02056873: Tourette Syndrome Deep Brain Stimulation
Official title: The Human Thalamocortical Network in Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tourette Syndrome
Keywords: deep brain stimulation
DBS
tourette
tourette's
tourette syndrome
TS
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Medtronic
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2014-02-06
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 criteria: Inclusion Criteria:

* 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)

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

Primary outcomes:
measure: Number of Participants With a 40% Reduction in Total Tics on the Yale Global Tic Severity Scale (YGTSS) With CDBS (Period 1)
timeFrame: Baseline to 6 months post-surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Michael Okun, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.