Clinical trial NCT01817517: Thalamic Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome
Official title: Phase 1 Study of Thalamic Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Tourette Syndrome
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2013-03-25
Enrollment: 10
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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 3. and 6. 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.
2. 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.
3. 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:

   1. 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.
   2. 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.
4. 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.
5. 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 18. 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.
6. 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.
7. Subject must be ambulatory.
8. Females who are postmenopausal, physically incapable of childbearing, or practicing an acceptable method of birth control. Acceptable methods of birth control include surgical sterilization, hormonal contraceptives, or double-barrier methods (condom or diaphragm with a spermicidal agent or intrauterine device \[IUD\]). If practicing an acceptable method of birth control, a negative urine pregnancy test result has been obtained at baseline Visits 1 and 3.
9. Subject is determined by an independent psychiatrist with expertise in capacity assessments to have decision-making capacity to provide informed consent.
10. Subject is able to read English, understand and cooperate with study procedures, and has signed a written informed consent form prior to any study procedures.

Exclusion Criteria:

1. Subject has a positive urine drug screen at any of the three Baseline Visits.
2. Subject had major surgery within three months prior to Baseline Visit 1 or has other surgery planned during the proposed study period.
3. Subject is determined by medical consultant to have medical contraindications to undergoing surgery.
4. Subject is pregnant or breast-feeding.
5. Subject has a history of alcohol or drug abuse within the past 6 months and/or dependence within the past year.
6. Subject has a medical illness/condition, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient.
7. Subject has an untreated or uncontrolled Axis I disorder or other major psychiatric disorder including major depression, bipolar disorder, or schizophrenia as determined by the screening psychiatrist.
8. Subject has either a current or past history of suicidal plan and/or intent.
9. Subject has a tic disorder or other movement disorder attributable to another medical, neurological, or psychiatric disorder other than Tourette Syndrome.
10. Subject has a drug-induced tic disorder.
11. Subject has significant psychosocial factors that might increase the risk of the DBS procedure or complicate recovery and outcome assessments. (Examples include - history of noncompliance with previous medical and psychosocial treatments, multiple failed medication treatments of inadequate dose or duration, a history of multiple other surgical procedures with poor outcome, unexplained medical history gaps, or pending lawsuits or other legal action.)
12. Subject has metal in the head or any other type of implanted stimulator (i.e. cardiac pacemaker, deep brain stimulator for a different disease, spinal cord stimulator, cochlear implant, vagus nerve stimulator, etc.).
13. Subject has participated in another investigational drug trial or therapeutic trial within 30 days of Baseline Visit 1.
14. Subject has a diagnosis of intellectual disability with documented IQ\<70.
15. Subject has a neurological condition, or a history of traumatic brain injury associated with loss of consciousness of \> 1 hour and/or intracranial/epidural/subdural bleeding.

Primary outcomes:
measure: Change from baseline in the Yale Global Tic Severity Scale (YGTSS)
timeFrame: 1 year after neurostimulator implantation.
measure: Incidence of adverse device effects (ADEs).
timeFrame: 1 year after neurostimulator implantation.
Secondary outcomes:
measure: Change from baseline in the Yale-Brown Obsessive Compulsive Scale
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the WHO Adult ADHD Self-Report Scale (ASRS)
timeFrame: 1 year after neurostimulator implantation.
Other outcomes:
measure: Change from baseline in the Grooved Pegboard test
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the Judgement of Line Orientation
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the Trailmaking Test A&B
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the Hopkins Verbal Learning Test
timeFrame: 1 year after neurostimulator implantation.
measure: Change from baseline in the Verbal Fluency Test (COWAT)
timeFrame: 1 year after neurostimulator implantation.
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: The Johns Hopkins University School of Medicine, Kennedy Krieger Institute
name: Shannon L Dean, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: