Tourette Syndrome Deep Brain Stimulation

NCT ID: NCT02056873

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-20
• Study Completion Date: 2023-08-24

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.

Conditions

Tourette Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuous 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.

Group Type: EXPERIMENTAL

Continuous DBS

Intervention Type: DEVICE

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.

Responsive Brain Stimulation (RBS Setting)

Eligible participants from Arm 1 will be switch to the RBS intervention.

Group Type: EXPERIMENTAL

Responsive Brain Stimulation (RBS Setting)

Intervention Type: DEVICE

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.

Interventions

Continuous DBS

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.

Intervention Type: DEVICE

Responsive Brain Stimulation (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.

Intervention Type: DEVICE

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

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Okun, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36094652 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://movementdisorders.ufhealth.org/

UF Center for Movement Disorders \& Neurorestoration

Other Identifiers

R01NS096008

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1553482

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OCR20343

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201300850 -A-N

Identifier Type: -

Identifier Source: org_study_id