Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression

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Brief Title

Tourette Deep Brain Stimulation (DBS) Target Detection & Suppression

Official Title

Defining Targets for Tic Detection and Suppression in Tourette Syndrome Deep Brain Stimulation

Brief Summary

      The investigators will implant and monitor 8 research subjects with a subcortical closed-loop
      system for detection and suppression of tics. The project will use the FDA-approved
      "Medtronic Percept PC" device, which is an implantable neurostimulator capable of recording
      neural signals. The study will target the CM nucleus of the thalamus and the aGPi in each
      brain hemisphere from each subject and we will connect the two leads placed in each brain
      hemisphere to two Percept devices.
    

Detailed Description

      Tourette syndrome (TS) is a continuous lifelong disabling condition that is highly prevalent
      and socially embarrassing.

      DBS has emerged as a promising treatment option for addressing uncontrollable tics in
      medically resistant and severe cases of TS frequently involving self-injurious behavior. The
      investigators have undertaken a major informatics initiative by establishing the
      International TS DBS Registry and Database, a multi-country consortium that has captured long
      term outcomes of 277 TS DBS patients representing 50-75% of the worldwide population. From
      these outcomes, two deep brain targets have emerged as potentially effective: the
      centromedian nucleus region (CM) of the thalamus, and the anterior globus pallidus internus
      (aGPi). However, the current understanding of tic generation is limited by many factors
      including a lack of animal models for TS, normal brain structure as revealed by structural
      imaging, and the impracticality of studying involuntary motor tics with functional imaging.
      Next generation closed-loop DBS systems can record brain activity in patients with TS and
      identify the neurophysiological correlates of tics. Moreover, these devices can deliver
      stimulation in response to a patient's symptomatic state. Our overall goal is to develop
      neurophysiology driven and connectivity-guided closed-loop DBS systems for the improved
      treatment of TS.
    


Study Type

Interventional


Primary Outcome

Yale Global Tic Severity Scale_(YGTSS) - Total Tic Score


Condition

Tourette Syndrome

Intervention

Medtronic Percept Neurostimulator

Study Arms / Comparison Groups

 Medtronic Percept Neurostimulator
Description:  This is a deep brain stimulator that can also record brain signals and deliver stimulation through a control algorithm based on brain activity.

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

8

Start Date

June 20, 2022

Completion Date

August 31, 2026

Primary Completion Date

August 31, 2026

Eligibility Criteria

        Inclusion Criteria:

          -  The diagnosis of TS must be made by both a fellowship-trained movement disorders
             neurologist and a psychiatrist and must meet Diagnostic and Statistical Manual of
             Mental Disorders (DSM-V) criteria for a diagnosis of TS.

          -  Yale Global Tic Severity Scale (YGTSS; 100) must be >35/50 and the motor tic subscore
             >15. The TS must be causing incapacitation with severe distress, self-injurious
             behavior, and/or quality of life disruption. Obsessive Compulsive Disorder (OCD),
             Depression, and Attention Deficit Hyperactivity Disorder (ADHD) are not
             exclusionary4-6 provided tics are the major difficulty requiring surgical
             intervention.

          -  There are no gender criteria for this study.

          -  The subject's TS symptoms must be medication refractory. To meet the medication
             refractory criteria, subjects must have been treated by a psychiatrist or neurologist
             experienced in TS with therapeutic doses (doses adapted from Scahill's recommendations
             of at least three dopamine blocking drugs5) either 1-4 mg/day of haloperidol, 2-8
             mg/day of pimozide, risperidone (1-3 mg/day), or aripiprazole (2.5-5 mg/day)]. There
             must be at a minimum7 single trial with an alpha-2 adrenergic agonist (0.1-0.3
             mg/day).

          -  Clinically relevant depression if present must be pharmacologically treated and deemed
             stable (by the study psychiatrist).

          -  Must have been stabilized for one 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 three 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 a subject did not have it prior to enrollment. Subjects are not
             required to participate in HRT but it will be highly encouraged, and must be completed
             prior to the start of the protocol. Those who improve significantly with HRT will be
             excluded from receiving surgery.

          -  If the 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 subject responds satisfactorily to botulinum toxin, and their
             quality of life significantly improves, they will be excluded.

          -  Must be 18 years of age or older

        Exclusion Criteria:

          -  Any previous neurosurgical 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 may impart an increased risk.

          -  The presence of only simple motor tics, a movement disorder other than TS, or
             medication related movement disorders from TS medications.

          -  The presence of drug-induced tics (potentially associated with the use of stimulant
             medications, anticonvulsant drugs, etc).

          -  Severe medical co-morbidity including cardiovascular disorder, lung disorder, kidney
             disease, chronic neurological disease, hematological disease, or frailty that impact
             tolerability of the surgery as judged by the screening physicians.

          -  Abnormal brain magnetic resonance imaging (MRI) scan including 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. Also excluded if severe atrophy is present on the brain scan.

          -  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 six months.

          -  Significant substance abuse or dependence (e.g., stimulants, alcohol, opiates,
             benzodiazepines) within the past six months.

          -  Multiple failed medication treatments of inadequate dose or duration.

          -  History of noncompliance with previous medical and psychosocial treatment efforts.

          -  Severe head banging tics (any tics which have the potential to result in damage to the
             DBS as judged by the neurosurgeon).

          -  Women of child-bearing potential who are pregnant or who wish to become pregnant
             during the study (a urine pregnancy screen required).

          -  History of multiple surgical procedures with poor outcomes.

          -  Unexplained gaps in medical history.

          -  Pending lawsuits or other legal action.
      

Gender

All

Ages

18 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

Michael Okun, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05371041

Organization ID

IRB202102161

Secondary IDs

UH3NS119844

Responsible Party

Sponsor

Study Sponsor

University of Florida

Collaborators

 National Institute of Neurological Disorders and Stroke (NINDS)

Study Sponsor

Michael Okun, MD, Principal Investigator, University of Florida


Verification Date

June 2022