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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deep Brain Stimulation implant | Experimental | Unblinded treatment arm, thalamic DBS for Tourette syndrome. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Medtronic Activa Deep Brain Stimulation System | Device |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) | 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. | 1 year after neurostimulator implantation |
| Number of Participants Free of Adverse Device Effects (ADEs). | 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. | 1 year after neurostimulator implantation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Yale-Brown Obsessive Compulsive Scale | We will assess deep brain stimulation effects on obsessive compulsive disorder symptoms using the Yale-Brown Obsessive Compulsive Scale (Baseline score - Final score). Score range 0-40, higher scores indicate greater severity of OCD symptoms. | 1 year after neurostimulator implantation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Grooved Pegboard Test | We will assess deep brain stimulation effects on Grooved Pegboard test as a part of the neurocognitive assessment of this group of Tourette syndrome patients. We will measure change in seconds 1y after stimulation activation (of the dominant hand). | 1 year after neurostimulator implantation. |
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 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.
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:
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 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.
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.
Subject must be ambulatory.
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.
Subject is determined by an independent psychiatrist with expertise in capacity assessments to have decision-making capacity to provide informed consent.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Ankur Butala, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Deep Brain Stimulation Implant | Unblinded treatment arm, thalamic DBS for Tourette syndrome. Medtronic Activa Deep Brain Stimulation System |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Deep Brain Stimulation Implant | Unblinded treatment arm, thalamic DBS for Tourette syndrome. Medtronic Activa Deep Brain Stimulation System |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) | 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. | values are per participant | Posted | Number | Score on a scale | 1 year after neurostimulator implantation |
|
|
Immediately post implantation up to study termination (approximately 6 years 4 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Deep Brain Stimulation Implant | Unblinded treatment arm, thalamic DBS for Tourette syndrome. Medtronic Activa Deep Brain Stimulation System |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lead Fracture | Product Issues | Non-systematic Assessment | DBS Electrode Fracture / Abnormal System Impedances |
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The study had recruitment limitations (both screened for consideration and implantations), partly due to staffing and administrative issues, which hampered analysis at a group level. Therefore, individual results were reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ankur Butala MD | Johns Hopkins Medicine | 410-502-0133 | Ankur.Butala@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 24, 2021 | Sep 4, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 25, 2021 | Sep 4, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D005879 | Tourette Syndrome |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Change From Baseline in the WHO Adult ADHD Self-Report Scale (ASRS) | We will assess deep brain stimulation effects on ADHD symptoms as measured by the WHO Adult ADHD Self-Report Scale (ASRS). | 1 year after neurostimulator implantation. |
| Change From Baseline in the Judgement of Line Orientation |
We will assess deep brain stimulation effects on the Judgement of Line Orientation test as a part of the neurocognitive assessment of this group of Tourette syndrome patients. |
| 1 year after neurostimulator implantation. |
| Change From Baseline in the Trailmaking Test - A | We will assess deep brain stimulation effects on the Trailmaking Test (A) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. | 1 year after neurostimulator implantation. |
| Change in Trail Making Test - B | Change in seconds at 1 year on the Trail Making Test - Part B (Baseline score - Final Score). The Time on Trails B (TMT) is scored by recording the number of seconds to complete each part of the test, with greater time indicating greater impairment. Normative ranges are used for interpretation and are stratified by age and education. TMT-B is an alternating alphabetical and numeral sequence. For TMT-B, the average is around 75 seconds, and a deficient score can be over 273 seconds. | 1year |
| Change From Baseline in the Hopkins Verbal Learning Test | We will assess deep brain stimulation effects on the change Hopkins Verbal Learning Test (delayed recall) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. Note, a positive value indicates an improvement, a negative number worsening. | 1 year after neurostimulator implantation. |
| Change From Baseline in the Verbal Fluency Test (COWAT) | We will assess deep brain stimulation effects on the change of Verbal Fluency Test (COWAT) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. Note, a positive value indicates an improvement, a negative number worsening. | 1 year after neurostimulator implantation. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Yale Global Tic Severity Scale (YGTSS) Total Score | The Yale Global Tic Severity Scale (YGTSS) is clinician-administered used to assess severity of tics over the past week in individuals with Tourette Syndrome and other tic disorders. It evaluates motor and phonic tics across several dimensions-number, frequency, intensity, complexity, interference. Scores are combined to create Total Motor Tic score, Total Phonic Tic score, and combined Total Tic score, and separate Impairment scale providing a comprehensive measure of tic severity and impact on daily life. Total score range 0- 100. Higher score suggests worse severity of tics. | value for each subject is reported | Number | units on a scale |
|
| Yale Brown Obsessive Compulsive Score | The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used clinical assessment tool for measuring the severity of obsessive-compulsive disorder (OCD) symptoms. The Y-BOCS consists of 10 items, 5 for obsessions and 5 for compulsions. Each item is rated on a 0-4 scale, with 0 indicating no symptoms and 4 indicating severe symptoms. A score range of 0-40. Higher is worse. | value for each subject is reported | Number | units on a scale |
|
| WHO Adult ADHD Self-Report Scale (ASRS) | Total score range from 0 to 54. A higher score corresponds to a worse severity of ADHD | value for each subject is reported | Number | units on a scale |
|
| Grooved Pegboard Test - Dominant Hand | The subject must place pegs shaped like keys into a board containing recesses that are oriented in randomly varying directions. The test is administered twice, once with the right and once with the left hand. Scores are time to completion in seconds for each hand and errors for each hand defined as number of pegs dropped during performance of the task. Lower scores (i.e. shorter duration in seconds) is preferred with normative data for age-matched controls. | value for each subject is reported | Number | seconds |
|
| Judgement of Line Orientation | The Judgment of Line Orientation (JLO) test is a neuropsychological test that measures visuospatial skills, specifically the ability to judge and match the angles of lines. The test requires visually comparing and matching angled lines with an array of 11 choices. Two points are awarded for correctly identifying both target lines, for a total score range of 0-30 points. A higher score indicates better visuospatial ability, while a lower score suggests a deficit. | value for each subject is reported | Number | score on a scale |
|
| Time on Trail Making Test (TMT- A) | The Time on Trails A (TMT) is scored by recording the number of seconds to complete each part of the test, with greater time indicating greater impairment. Normative ranges are used for interpretation and are stratified by age and education. TMT-A is an alphabetical sequence. A common benchmark for TMT-A is an average time of around 29 seconds, with a deficient score often considered to be over 78 seconds. | value for each subject is reported | Number | seconds |
|
| Time on Trail Making Test (TMT-B) | The Time on Trails B (TMT) is scored by recording the number of seconds to complete each part of the test, with greater time indicating greater impairment. Normative ranges are used for interpretation and are stratified by age and education. TMT-B is an alternating alphabetical and numeral sequence. For TMT-B, the average is around 75 seconds, and a deficient score can be over 273 seconds. | value for each subject is reported | Number | seconds |
|
| Hopkins Verbal Learning Test - Delayed Free Recall | The Hopkins Verbal Learning Test-Revised (HVLT-R) is a brief, standardized neuropsychological test used to assess verbal memory and learning by having an individual recall and recognize a list of 12 words. It evaluates immediate recall, delayed recall, and delayed recognition over a 25-minute interval and is particularly useful for screening for memory problems. The total score range is 0 - 12, where 12 items were successfully and spontaneously recalled after 25 minutes. | value for each subject is reported | Number | items recalled |
|
| Verbal Fluency Test (COWAT) | The Controlled Oral Word Association Test (COWAT) is a verbal fluency test that assesses spontaneous word production. The COWAT is scored by tallying the total number of acceptable generated within 60 seconds for three letters (e.g., F, A, S). The lowest possible score is zero, There is no limit to the higher end of the scale given that participants can produce as many words as possible for each of the three letters. Higher scores indicate greater word retrieval and better cognitive function | value for each subject is reported | Number | total # of words (FAS) |
|
| Counts |
|---|
| Participants |
|
|
| Primary | Number of Participants Free of Adverse Device Effects (ADEs). | 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. | Posted | Count of Participants | Participants | 1 year after neurostimulator implantation. |
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|
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| Secondary | Change From Baseline in the Yale-Brown Obsessive Compulsive Scale | We will assess deep brain stimulation effects on obsessive compulsive disorder symptoms using the Yale-Brown Obsessive Compulsive Scale (Baseline score - Final score). Score range 0-40, higher scores indicate greater severity of OCD symptoms. | values are per participant | Posted | Number | score on a scale | 1 year after neurostimulator implantation. |
|
|
|
| Secondary | Change From Baseline in the WHO Adult ADHD Self-Report Scale (ASRS) | We will assess deep brain stimulation effects on ADHD symptoms as measured by the WHO Adult ADHD Self-Report Scale (ASRS). | values are per participant | Posted | Number | score on a scale | 1 year after neurostimulator implantation. |
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| Other Pre-specified | Change From Baseline in the Grooved Pegboard Test | We will assess deep brain stimulation effects on Grooved Pegboard test as a part of the neurocognitive assessment of this group of Tourette syndrome patients. We will measure change in seconds 1y after stimulation activation (of the dominant hand). | Participants with data collected | Posted | Number | seconds (reduction) | 1 year after neurostimulator implantation. |
|
|
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| Other Pre-specified | Change From Baseline in the Judgement of Line Orientation | We will assess deep brain stimulation effects on the Judgement of Line Orientation test as a part of the neurocognitive assessment of this group of Tourette syndrome patients. | Posted | Number | score on a scale | 1 year after neurostimulator implantation. |
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| Other Pre-specified | Change From Baseline in the Trailmaking Test - A | We will assess deep brain stimulation effects on the Trailmaking Test (A) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. | Posted | Number | seconds | 1 year after neurostimulator implantation. |
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| Other Pre-specified | Change in Trail Making Test - B | Change in seconds at 1 year on the Trail Making Test - Part B (Baseline score - Final Score). The Time on Trails B (TMT) is scored by recording the number of seconds to complete each part of the test, with greater time indicating greater impairment. Normative ranges are used for interpretation and are stratified by age and education. TMT-B is an alternating alphabetical and numeral sequence. For TMT-B, the average is around 75 seconds, and a deficient score can be over 273 seconds. | Not Posted | 1year | Participants |
| Other Pre-specified | Change From Baseline in the Hopkins Verbal Learning Test | We will assess deep brain stimulation effects on the change Hopkins Verbal Learning Test (delayed recall) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. Note, a positive value indicates an improvement, a negative number worsening. | Posted | Number | change # of items recalled | 1 year after neurostimulator implantation. |
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| Other Pre-specified | Change From Baseline in the Verbal Fluency Test (COWAT) | We will assess deep brain stimulation effects on the change of Verbal Fluency Test (COWAT) as a part of the neurocognitive assessment of this group of Tourette syndrome patients. Note, a positive value indicates an improvement, a negative number worsening. | Posted | Number | change in total # of words (FAS) | 1 year after neurostimulator implantation. |
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| 1 |
| 2 |
| 1 |
| 2 |
| 0 |
| 2 |
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| Meningoencephalitis | Nervous system disorders | Non-systematic Assessment |
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| D013981 | Tic Disorders |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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