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The purpose of this trial is to determine whether a particular type of Deep Brain Stimulation (DBS), scheduled Deep Brain stimulation (SBS), is an effective and safe treatment for Tourettte syndrome (TS).
The trial will also examine the brain activity associated with TS and tics and explore the possibility of responsive brain stimulation (RBS).
DBS is a surgical procedure that seeks to change the brain's electrical signalling by means of applied electrical current. To this end, a wire with tiny stimulating electrodes is implanted into one or both sides of the brain. An electrode is a small piece of metal used to take an electric current to or from a power source. These electrodes are connected under the skin on the scalp to a small electrical unit called an INS (implantable neurostimulator), which is similar to a heart pacemaker. The device sends out electrical impulses that appear to change the normal flow of electricity in the brain.
The wires which house the electrodes will be implanted on both sides of the brain oriented towards the centromedian thalamus-parafascicular complex. This region of the brain has to date the greats number of documented cases revealing significant improvements in motor tics.
This region of the brain will also provide a target where physiological changes related to motor tics are likely to be discovered.
The device we propose for this study has several features that make it more suitable for use in the TS population than other devices. It is self-contained in the skull and brain, and contains no tunneled neck connector wire and no chest pacemaker deice. This will help to lessen infection, and will assist in limiting device-related fractures due to tics involving neck region. Also, the system can record electro-encephalograph data from the area of the electrodes, which will assist us in gathering information about what specific physiological changes are correlated with tics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Delayed Activation - Deep Brain Stimulation (DBS) | Active Comparator | Delayed Activation stimulation in which no electrical charge is delivered through the Neuropace RNS (responsive neurostimulation) system for the first 59 days. On Day 60, all subjects will be programmed to receive active stimulation.
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| Immediate Activation - Deep Brain Stimulation (DBS) | Active Comparator | Active stimulation through the Neuropace RNS (responsive neurostimulation) system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NeuroPace RNS® System Deep Brain Stimulator | Device | Utilizes a signal that the device detects and will respond to with an electrical pre-defined pulse if the signal is encountered. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Yale Global Tic Severity Scale (YGTSS) Scores From Baseline to 6 Months Across All Study Participants Presented | The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are:
The YGTSS Total Score is obtained by adding the Total Tic Score to the Overall Impairment Rating. The efficacy of the intervention will be assessed by comparing each subject's 6-month YGTSS Total Score to the pre-operative value for the same patient. Efficacy is considered 50% or greater reduction in this score. | Baseline to 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Tics and Neural Physiology | Electrical recordings of electroencephalography activity were taken from each subject's implanted leads at each visit from baseline to 6 months. At baseline, the recordings were taken with the device in the off state (not stimulating), while at the 6 month visits the recordings were taken with the subject's device set to optimal parameters for tic control. Using Pearson's correlation coefficient, the variations in frequency and power which were observed were correlated with the Yale Global Tic Severity (YGTSS) scores obtained during primary outcome testing. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Okun, MD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida Movement Disorders Center | Gainesville | Florida | 32611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23044532 | Derived | Okun MS, Foote KD, Wu SS, Ward HE, Bowers D, Rodriguez RL, Malaty IA, Goodman WK, Gilbert DM, Walker HC, Mink JW, Merritt S, Morishita T, Sanchez JC. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013 Jan;70(1):85-94. doi: 10.1001/jamaneurol.2013.580. |
| Label | URL |
|---|---|
| Increased Thalamic Gamma Band Activity Correlates with Symptom Relief following Deep Brain Stimulation in Humans with Tourette's Syndrome | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Delayed Activation DBS | Sham stimulation in which no electrical charge is delivered through the Neuropace RNS system. By Day 60, all subjects will be programmed to receive active stimulation.
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| FG001 | Immediate Activation DBS | Active stimulation through the Neuropace RNS system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects
|
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Delayed Activation DBS | Sham stimulation in which no electrical charge is delivered through the Neuropace RNS system. By Day 60, all subjects will be programmed to receive active stimulation.
|
| 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 | Mean Change in Yale Global Tic Severity Scale (YGTSS) Scores From Baseline to 6 Months Across All Study Participants Presented | The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are:
The YGTSS Total Score is obtained by adding the Total Tic Score to the Overall Impairment Rating. The efficacy of the intervention will be assessed by comparing each subject's 6-month YGTSS Total Score to the pre-operative value for the same patient. Efficacy is considered 50% or greater reduction in this score. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline to 6 Months |
|
Adverse event data was collected starting the day of the screening visit and continuing through each subject's 2 year follow-up visit.
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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 | Sham DBS | Sham stimulation in which no electrical charge is delivered through the Neuropace RNS system. NeuroPace RNS® System Deep Brain Stimulator: • There will be a one month post-operative period during which stimulation is not turned on.
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Paresthesia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | During stimulation testing, varying configurations of settings would induce different sensations - tingling, numbness, pressure, cold and warmth. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Assistant Director of Clinical Trials | University of Florida Center for Movement Disorders & Neurorestoration | 352-294-5000 | stacy.merritt@neurology.ufl.edu |
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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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| ID | Term |
|---|---|
| D046690 | Deep Brain Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
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Prospective blinded staggered onset design
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Programming to be performed for this study by the programming investigator under the supervision of the PI
|
| Baseline to 6 Months |
| BG001 | Immediate Activation DBS | Active stimulation through the Neuropace RNS system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects
|
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
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Sham stimulation in which no electrical charge is delivered through the Neuropace RNS system. By Day 60, all subjects will be programmed to receive active stimulation.
|
| OG001 | Immediate Activation DBS | Active stimulation through the Neuropace RNS system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects
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| Secondary | Correlation of Tics and Neural Physiology | Electrical recordings of electroencephalography activity were taken from each subject's implanted leads at each visit from baseline to 6 months. At baseline, the recordings were taken with the device in the off state (not stimulating), while at the 6 month visits the recordings were taken with the subject's device set to optimal parameters for tic control. Using Pearson's correlation coefficient, the variations in frequency and power which were observed were correlated with the Yale Global Tic Severity (YGTSS) scores obtained during primary outcome testing. | Posted | Number | Pearson Correlation Coefficient | Baseline to 6 Months |
|
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| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Active DBS | Active stimulation through the Neuropace RNS system at settings to maximally reduce tic frequency & severity, while limiting potential stimulation-induced side-effects NeuroPace RNS® System Deep Brain Stimulator: • There will be a one month post-operative period during which stimulation is not turned on.
| 1 | 2 | 2 | 2 |
| Attempted suicide | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Stimulation-induced feelings of dizziness or lightheadedness |
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| Movements Involuntary | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Stimulation-induced pulling of the head or neck to one side or another. |
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| Dysarthria | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | During stimulation testing, a sudden inability to form words. |
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| Blurred vision | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Stimulation-induced abdominal uneasiness. |
|
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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 |