Tourette Syndrome Deep Brain Stimulation

Tourette Syndrome Clinical Trial

Official title:

The Human Thalamocortical Network in Tourette Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02056873
• Other study ID #: IRB201300850 -A-N
• Secondary ID: KL2TR00142915534
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 2014
• Est. completion date: June 30, 2023

Study information

• Verified date: June 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Syndrome
• Tourette Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (4)

Lead Sponsor	Collaborator
University of Florida	Medtronic, National Institutes of Health (NIH), National Science Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in total tics on the Yale Global Tic Severity Scale (YGTSS) after 6 months as an effect of centromedian (CM) continuous DBS stimulation	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.	Baseline to 6 months post-surgery
Primary	Correlation between increase in gamma oscillations and improvement in TS symptomatology	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.	Date of surgery until 24 months post-surgery
Primary	Responsive brain stimulation (RBS) as an effective alternative to continuous DBS stimulation	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.	Baseline until 24 months post-surgery
Primary	Reduction in total tics on the YGTSS after 24 months as an effect of centromedian (CM) continuous DBS stimulation	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.	Baseline to 24 months post-surgery

External Links

•   UF Center for Movement Disorders & Neurorestoration