Tourette SyndromeNCT02056873
Tourette Syndrome Deep Brain Stimulation
A study testing Continuous DBS and Responsive Brain Stimulation (RBS Setting) in people with Tourette Syndrome, run by University of Florida at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effectiveness and safety of deep brain stimulation (DBS) as a possible new treatment for Tourette Syndrome (TS). This investigation will (1) test the hypothesis that centromedian (CM) continuous brain stimulation will be an effective, safe method for the treatment of tics… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Tourette Syndrome
- What is being tested?
- Continuous DBS and Responsive Brain Stimulation (RBS Setting)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2014to 24 Aug 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be 21+ years of age
- Diagnosis of Tourette Syndrome (TS) in accordance to the Diagnostic and Statistical Manual of Mental DIsorders (DSM-V) criteria
- Yale Global Tic Severity Scale (YGTSS) must be ≥35/50 for at least 12 months; Motor Tic subscore must be ≥15
- TS must be causing incapacitation with severe distress, self-injurious behavior, and/or quality of life disruption
- TS must be medication refractory. Criteria to determine if medication refractory is the exact criteria stated by Mink et. al TSA DBS Guidelines published in 2006: Subjects must have been treated by a psychiatrist or neurologist experienced in TS with therapeutic doses of either 1-4 mg/day of haloperidol or 2-8 mg/day of pimozide, risperidone (1-3 mg/day), and aripiprazole (2.5-5 mg/day). Must be at minimum a single trial with an alpha-2 adrenergic agonist (0.1-0.3 mg/day)
- Clinically relevant depression must be pharmacologically treated and deemed stable
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- Must have been stabilized for 1 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 3 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 subject did not have it prior to enrollment. (Subjects not required to participate in HRT but it will be highly encouraged, and must be completed prior to start of this study's protocol. Those who improve significantly will be excluded from receiving DBS surgery)
- If 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 patient responds satisfactorily and their quality of life significantly improves, they will be excluded)
Who cannot join
- Any previous neurological 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 can cause increased risk
- The presence of only simple motor tics, a movement disorder other than TS, or medication related movement disorders from TS medications
- Severe medical co-morbidity including cardiovascular disorder, lung disorder, kidney disease, chronic neurological disease, hematological disease, or frailty that impacts tolerability of the surgery as judged by the screening physicians
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- Abnormal brain magnetic resonance imaging (MRI) scan, including severe atrophy, 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
- 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 6 months
- Significant substance abuse or dependence within the last 6 months
- Multiple failed medication treatments of inadequate dose or duration
- History of noncompliance with previous medical and psychosocial treatment efforts
- Severe head banging tics
- Women of child-bearing potential who are pregnant or planning pregnancy (urine pregnancy test required)
- Positive urine drug screen for illicit substances (urine drug screen required)
- History of multiple surgical procedures with poor outcomes
- Unexplained gaps in medical history
- Pending lawsuits or other legal action
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Human Thalamocortical Network in Tourette Syndrome
The purpose of this study is to evaluate the effectiveness and safety of deep brain stimulation (DBS) as a possible new treatment for Tourette Syndrome (TS).
This investigation will (1) test the hypothesis that centromedian (CM) continuous brain stimulation will be an effective, safe method for the treatment of tics in medication refractory TS, (2) will define the intra-operative and post-operative physiological changes, and (3) will test the hypothesis that responsive brain stimulation (RBS) will provide an alternative to chronic DBS in TS.
Read the detailed description
Normal clinical care for TS includes cognitive behavior therapy, medication, supportive psychotherapy, and/or a combination of the two. To meet entry criteria for this study, you must have already tried these methods and they did not help your symptoms. DBS is considered experimental for the treatment of TS and would not be done as normal clinical care.
Participation in this study will require extensive pre-surgical screening to determine eligibility for DBS surgery, a DBS surgical procedure, and regular follow-ups. Subjects will be seen monthly post surgery for 6 months. After 6 months, data will be assessed and RBS may be offered as a stimulation setting. If so, the stimulator settings will be changed from chronic to responsive. If not, the subject will continue to receive chronic DBS stimulation. Subsequent visits will be scheduled every 6 months until a total of 24 months of study participation.
At the end of the initial 24-month study period, subjects will have the choice of 1) continuing active stimulation at the current setting, 2) continuing stimulation but searching for a new setting, 3) discontinuing stimulation (turning the device off), 4) having the device removed. If the subject continues to receive active stimulation, they will be followed by the PI and seen at yearly intervals until the DBS system is commercially available, FDA approved for the treatment of TS, or unavailable for patient use.
- Conditions
- Tourette Syndrome
- Being tested
- Continuous DBS, Responsive Brain Stimulation (RBS Setting)
- Keywords
- deep brain stimulation, DBS, tourette, tourette's, tourette syndrome, TS
- Medical subject headings
- Tourette Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous DBSDevice
Also called Neurostimulator: Medtronic Activa PC+S Device Model 37604, CM thalamic leads: Medtronic Leads Model 3387, ECOG strip leads: The Resume II Medtronic Model 3587A
The DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips.
The DBS system will be set to provide continuous stimulation for the 6 months following surgery. Subjects will be seen monthly for evaluation as a part of normal clinical care for DBS. At 6 months, the investigators will determine whether or not the subject is a candidate for responsive brain stimulation (RBS). Qualifying subjects will have the option to have their settings changed in order to participate in the RBS stimulation intervention. Subjects who do not qualify or do not participate will continue to receive this intervention for the duration of the study. These subjects will been seen every 6 months for evaluation as part of normal clinical care for DBS.
Responsive Brain Stimulation (RBS Setting)Device
Also called Neurostimulator: Medtronic Activa PC+S Device Model 37604, CM thalamic leads: Medtronic Leads Model 3387, ECOG strip leads: The Resume II Medtronic Model 3587A
The DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips.
Six months post-surgery, the DBS system will be set to provide responsive stimulation for the duration of the study. Subjects will be seen every 6 months for evaluation as a part of normal clinical care for DBS.
Data gathered from the subject during the first 6 months will be used to determine if this intervention is applicable for each individual subject. Subjects who do not qualify will continue to receive the other study intervention.
| Study group | Role | What they receive |
|---|---|---|
| Continuous Deep Brain Stimulation (DBS) | Experimental | Subjects' DBS surgical intervention requires implantation of a DBS system: two CM thalamic leads (one in each brain hemisphere), two ECOG strip leads (one in each brain hemisphere), and two neurostimulators implanted in the chest.
The ECOG strip lead is implanted into the brain to provide an interface through which stimulation can be delivered or activity of the brain can be monitored by the device, or observed by a clinician using a programmer.
Neurostimulator and leads system includes a programmer, which includes a wand and telemetry interface, and a patient remote control to check battery status and whether the device is on or off. The programmer is used to set up the device, including setup of stimulation and recording, as well as to retrieve data for subsequent review. Receives: Device: Continuous DBS |
| Responsive Brain Stimulation (RBS Setting) | Experimental | Eligible participants from Arm 1 will be switch to the RBS intervention. Receives: Device: Responsive Brain Stimulation (RBS Setting) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a 40% Reduction in Total Tics on the Yale Global Tic Severity Scale (YGTSS) With CDBS (Period 1)
The Yale Global Tic Severity Scale (YGTSS) is a 10-item semi-structured clinician-rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The items pertaining to the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. The total scale has been used in this study and has a range of 0-50. A higher score indicates a higher severity of symptoms.
Patients reach the outcome measure with a 40% reduction of YGTSS at month 6 post-op compared to baseline (i.e., 40% improvement in their tic severity scale).
Measured: Baseline to 6 months post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2014 (estimated)
- Study start20 Mar 2014
- Primary completion25 Aug 2021
- Study completion24 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tourette SyndromeStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Michael Okun, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02056873
- Sponsor's protocol ID
- IRB201300850 -A-N
- Other IDs
- R01NS096008, 1553482, OCR20343
- Status last verified
- Aug 2024
- First submitted
- 3 Feb 2014
- Last updated
- 5 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Cagle JN, Okun MS, Cernera S, Eisinger RS, Opri E, Bowers D, Ward H, Foote KD, Gunduz A. Embedded Human Closed-Loop Deep Brain Stimulation for Tourette Syndrome: A Nonrandomized Controlled Trial. JAMA Neurol. 2022 Oct 1;79(10):1064-1068. doi: 10.1001/jamaneurol.2022.2741.
PubMed 36094652
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Human Thalamocortical Network in Tourette Syndrome
- ClinicalTrials.gov ID
- NCT02056873
- Acronym / sponsor ID
- IRB201300850 -A-N
- Conditions
- Tourette Syndrome
- Keywords
- deep brain stimulation, DBS, tourette, tourette's, tourette syndrome, TS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Medtronic, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 20 Mar 2014 (actual)
- Primary completion
- 25 Aug 2021 (actual)
- Study completion
- 24 Aug 2023 (actual)
- First posted
- 6 Feb 2014 (estimated)
- Results
- Posted 5 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effectiveness and safety of deep brain stimulation (DBS) as a possible new treatment for Tourette Syndrome (TS).
This investigation will (1) test the hypothesis that centromedian (CM) continuous brain stimulation will be an effective, safe method for the treatment of tics in medication refractory TS, (2) will define the intra-operative and post-operative physiological changes, and (3) will test the hypothesis that responsive brain stimulation (RBS) will provide an alternative to chronic DBS in TS.
Detailed description
Normal clinical care for TS includes cognitive behavior therapy, medication, supportive psychotherapy, and/or a combination of the two. To meet entry criteria for this study, you must have already tried these methods and they did not help your symptoms. DBS is considered experimental for the treatment of TS and would not be done as normal clinical care.
Participation in this study will require extensive pre-surgical screening to determine eligibility for DBS surgery, a DBS surgical procedure, and regular follow-ups. Subjects will be seen monthly post surgery for 6 months. After 6 months, data will be assessed and RBS may be offered as a stimulation setting. If so, the stimulator settings will be changed from chronic to responsive. If not, the subject will continue to receive chronic DBS stimulation. Subsequent visits will be scheduled every 6 months until a total of 24 months of study participation.
At the end of the initial 24-month study period, subjects will have the choice of 1) continuing active stimulation at the current setting, 2) continuing stimulation but searching for a new setting, 3) discontinuing stimulation (turning the device off), 4) having the device removed. If the subject continues to receive active stimulation, they will be followed by the PI and seen at yearly intervals until the DBS system is commercially available, FDA approved for the treatment of TS, or unavailable for patient use.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Deep Brain Stimulation (DBS) | Experimental | Device: Continuous DBSSubjects' DBS surgical intervention requires implantation of a DBS system: two CM thalamic leads (one in each brain hemisphere), two ECOG strip leads (one in each brain hemisphere), and two neurostimulators implanted in the chest. The ECOG strip lead is implanted into the brain to provide an interface through which stimulation can be delivered or activity of the brain can be monitored by the device, or observed by a clinician using a programmer. Neurostimulator and leads system includes a programmer, which includes a wand and telemetry interface, and a patient remote control to check battery status and whether the device is on or off. The programmer is used to set up the device, including setup of stimulation and recording, as well as to retrieve data for subsequent review. |
| Responsive Brain Stimulation (RBS Setting) | Experimental | Device: Responsive Brain Stimulation (RBS Setting)Eligible participants from Arm 1 will be switch to the RBS intervention. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must be 21+ years of age
- Diagnosis of Tourette Syndrome (TS) in accordance to the Diagnostic and Statistical Manual of Mental DIsorders (DSM-V) criteria
- Yale Global Tic Severity Scale (YGTSS) must be ≥35/50 for at least 12 months; Motor Tic subscore must be ≥15
- TS must be causing incapacitation with severe distress, self-injurious behavior, and/or quality of life disruption
- TS must be medication refractory. Criteria to determine if medication refractory is the exact criteria stated by Mink et. al TSA DBS Guidelines published in 2006: Subjects must have been treated by a psychiatrist or neurologist experienced in TS with therapeutic doses of either 1-4 mg/day of haloperidol or 2-8 mg/day of pimozide, risperidone (1-3 mg/day), and aripiprazole (2.5-5 mg/day). Must be at minimum a single trial with an alpha-2 adrenergic agonist (0.1-0.3 mg/day)
Key exclusion criteria (18 listed)
- Any previous neurological 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 can cause increased risk
- The presence of only simple motor tics, a movement disorder other than TS, or medication related movement disorders from TS medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous DBSAlso: Neurostimulator: Medtronic Activa PC+S Device Model 37604, CM thalamic leads: Medtronic Leads Model 3387, ECOG strip leads: The Resume II Medtronic Model 3587AThe DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips. The DBS system will be set to provide continuous stimulation for the 6 months following surgery. Subjects will be seen monthly for evaluation as a part of normal clinical care for DBS. At 6 months, the investigators will determine whether or not the subject is a candidate for responsive brain stimulation (RBS). Qualifying subjects will have the option to have their settings changed in order to participate in the RBS stimulation intervention. Subjects who do not qualify or do not participate will continue to receive this intervention for the duration of the study. These subjects will been seen every 6 months for evaluation as part of normal clinical care for DBS. | Device | Continuous Deep Brain Stimulation (DBS) |
| Responsive Brain Stimulation (RBS Setting)Also: Neurostimulator: Medtronic Activa PC+S Device Model 37604, CM thalamic leads: Medtronic Leads Model 3387, ECOG strip leads: The Resume II Medtronic Model 3587AThe DBS system includes an implantable neurostimulator, CM thalamic leads, and Electrocorticography (ECOG) strips. Six months post-surgery, the DBS system will be set to provide responsive stimulation for the duration of the study. Subjects will be seen every 6 months for evaluation as a part of normal clinical care for DBS. Data gathered from the subject during the first 6 months will be used to determine if this intervention is applicable for each individual subject. Subjects who do not qualify will continue to receive the other study intervention. | Device | Responsive Brain Stimulation (RBS Setting) |
Primary outcome
Number of Participants With a 40% Reduction in Total Tics on the Yale Global Tic Severity Scale (YGTSS) With CDBS (Period 1)
Time frame: Baseline to 6 months post-surgery
The Yale Global Tic Severity Scale (YGTSS) is a 10-item semi-structured clinician-rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The items pertaining to the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. The total scale has been used in this study and has a range of 0-50. A higher score indicates a higher severity of symptoms. Patients reach the outcome measure with a 40% reduction of YGTSS at month 6 post-op compared to baseline (i.e., 40% improvement in their tic severity scale).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36094652Cagle JN, Okun MS, Cernera S, Eisinger RS, Opri E, Bowers D, Ward H, Foote KD, Gunduz A. Embedded Human Closed-Loop Deep Brain Stimulation for Tourette Syndrome: A Nonrandomized Controlled Trial. JAMA Neurol. 2022 Oct 1;79(10):1064-1068. doi: 10.1001/jamaneurol.2022.2741.
- UF Center for Movement Disorders \& NeurorestorationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Okun, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Continuous DBS and Responsive Brain Stimulation (RBS Setting) in people with Tourette Syndrome, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a 40% Reduction in Total Tics on the Yale Global Tic Severity Scale (YGTSS) With CDBS (Period 1) (time frame: Baseline to 6 months post-surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02056873, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.