Brief Title
Tourette Syndrome Deep Brain Stimulation
Official Title
The Human Thalamocortical Network in Tourette Syndrome
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.
Study Type
Interventional
Primary Outcome
Reduction in total tics on the Yale Global Tic Severity Scale (YGTSS) after 6 months as an effect of centromedian (CM) continuous DBS stimulation
Condition
Tourette Syndrome
Intervention
DBS System
Study Arms / Comparison Groups
Deep Brain Stimulation (DBS)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Device
Estimated Enrollment
20
Start Date
May 2014
Completion Date
October 2021
Primary Completion Date
October 2021
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
Gender
All
Ages
21 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Michael Okun, MD, 352-733-2429, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02056873
Organization ID
IRB201300850 -A-N
Secondary IDs
KL2TR001429
Responsible Party
Sponsor
Study Sponsor
University of Florida
Collaborators
Medtronic
Study Sponsor
Michael Okun, MD, Principal Investigator, University of Florida
Verification Date
July 2021