Phase 1 Study of Thalamic Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome
Overview
- Phase
- N/A
- Intervention
- Medtronic Activa Deep Brain Stimulation System
- Conditions
- Tourette Syndrome
- Sponsor
- Johns Hopkins University
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Change From Baseline in the Yale Global Tic Severity Scale (YGTSS)
- Status
- Terminated
- Last Updated
- 3 months ago
Overview
Brief Summary
This research is being performed to try to understand if the use of deep brain stimulation or DBS can treat the symptoms of Tourette syndrome that do not respond well to current medications. In order to do this the investigators will place small stimulation leads on both sides of the brain in a region (a portion of the thalamus) that may alter the abnormal activity in the brain contributing to the symptoms of Tourette syndrome. This requires two surgical procedures, and several preoperative and postoperative visits for tuning the stimulation parameters and recording stimulation effects. The FDA has not approved DBS for use in people with Tourette syndrome, and Medtronic (the manufacturer of the device) has not conducted testing for the system in Tourette syndrome. Therefore its use in this study is experimental.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females who are \>=15 years of age. There is no strict age cutoff at the upper limit of inclusion, however subjects may meet the
Exclusion Criteria
- •based on medical contraindications to deep brain stimulation surgery (Points
- •under the Exclusion Criteria). For subjects in the age range of 15-24 years, an additional Ethics Committee consultation will be obtained prior to offering the subject the required screening visit. This is based on the revised screening criteria now proposed by Shrock, Mink, et al. on studies investigating DBS in TS. Additionally, for subjects in the age range of 15-20, a caregiver will be required to be present for all study visits.
- •Subject has a diagnosis of TS as determined by a review of medical records, discussion with referring psychiatrist as well as the DSM-IV criteria and videotaped assessment. This will include an assessment to determine the presence of psychogenic tics, embellishment, factitious symptoms, personality disorders and malingering.
- •Subject determined to be treatment-resistant for at least one year prior to the Screening Visit as demonstrated by clinical evidence (determined by review of medical records and discussion with referring psychiatrist or neurologist) of persistent functionally impairing tics that have not responded to treatment with a minimum of three adequate regimens of medication including two failed trials of at least one typical neuroleptic and one atypical neuroleptic medication, along with one failed trial of a first tier medication as defined as follows:
- •Adequate trials of one non-neuroleptic medication including drugs from the following (first tier) list: clonidine, guanfacine, topiramate, baclofen, levetiracetam, and clonazepam. Trial failure is defined as demonstrated lack of efficacy or severe side effects.
- •Two adequate trials of at least one typical neuroleptic medication (pimozide, fluphenazine, haloperidol) and at least one atypical neuroleptic (risperidone, aripiprazole, ziprasidone, olanzapine, quetiapine). Trial failure is defined as demonstrated lack of efficacy or severe side effects.
- •A mandatory trial of behavioral interventions in an attempt to reduce the severity of the tics or comorbid symptoms must also be completed by the subject before offering participation in this trial. This may include habit reversal therapies, stress reduction therapies, or other behavioral therapies under investigation for tic suppression.
- •Subject has both significant vocal and motor tics with a tic subscale score of at least 35 on the YGTSS (Yale Global Tic Severity Scale) at all three Baseline Visits prior to undergoing surgery. For subjects with predominantly vocal tics (and minimal motor) causing significant problems this score requirement will be reduced to 18, similarly for subjects with predominantly motor tics (and minimal vocal) causing significant problems the required score will be
- •A portion of the study team, including the surgeon and two neurologists, will determine by consensus which category the subject falls into and whether the tics are a significant problem.
- •All other aspects of the subject's care must be optimized during the preceding 6 months before admission to the study. This includes treatment for comorbid medical, neurological, and psychiatric disorders. Additionally, it includes psychological interventions for any ongoing psychosocial problems the subject may have during the preceding 6 months before study admission.
Arms & Interventions
Deep Brain Stimulation implant
Unblinded treatment arm, thalamic DBS for Tourette syndrome.
Intervention: Medtronic Activa Deep Brain Stimulation System
Outcomes
Primary Outcomes
Change From Baseline in the Yale Global Tic Severity Scale (YGTSS)
Time Frame: 1 year after neurostimulator implantation
Investigators will assess deep brain stimulation effects on tic frequency and severity using the change in Yale Global Tic Severity Scale (YGTSS) in this population of Tourette syndrome patients. The scales range from 0-100, higher scores indicate greater tic severity and impairment.
Number of Participants Free of Adverse Device Effects (ADEs).
Time Frame: 1 year after neurostimulator implantation.
We will assess the incidence of adverse device effects (ADEs) as defined by the Code of Federal Regulations (21 CFR 812.3) at 1 year. Number of participants free of adverse events by 1year post implantation is reported.
Secondary Outcomes
- Change From Baseline in the Yale-Brown Obsessive Compulsive Scale(1 year after neurostimulator implantation.)
- Change From Baseline in the WHO Adult ADHD Self-Report Scale (ASRS)(1 year after neurostimulator implantation.)