- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02911103
Deep Brain Stimulation Surgery for Focal Hand Dystonia
Deep Brain Stimulation Surgery for Treatment of Focal Hand Dystonia
Researchers want to test a procedure called deep brain simulation (DBS) to treat focal hand dystonia (FHD). A device called a neurostimulator is placed in the chest. It is attached to wires placed in brain areas that affect movement. Stimulating these areas can help block nerve signals that cause abnormal movements.
Objectives:
To test DBS as treatment for FHD. To learn about brain and nerve cell function in people with dystonia.
Eligibility:
People ages 18 and older with severe FHD who have tried botulinum toxin treatment at least twice
Design:
Participation lasts 5 years.
Participants will be screened with:
Medical history
Physical exam
Videotape of their dystonia
Blood, urine, and heart tests
Brain MRI scan
Chest X-ray
Neuropsychological tests: answering questions, doing simple actions, and taking memory and thinking tests.
Hand movement tests
Participants will have surgery: A frame fixes their head to the operating table. A small hole is made in the skull. Wires are inserted to record brain activity and stimulate the brain while they do simple tasks. The wires are removed and the DBS electrode is inserted into the hole. The neurostimulator is placed under the skin of the chest, with wires running to the electrode in the brain. They will have CT and MRI scans during surgery.
Participants will recover in the hospital for about 1 week.
The neurostimulator will be turned on 1 4 weeks after discharge. Participants will have regular visits until the study ends. Visits include:
Checking symptoms and side effects
MRI
Movement, thinking, and memory tests
If the neurostimulator s battery runs out, participants will have surgery to replace it.
...
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Objectives
To confirm the safety and possible trends toward efficacy of thalamic deep brain stimulation (DBS) targeting the ventralis oralis anterior/ventralis oralis posterior (VOA/VOP) nuclear complex in the treatment of subjects with focal hand dystonia (FHD); and to study the electrophysiologic properties of neurons in the VOA/VOP complex. DBS is FDA approved for Parkinson s disease, Essential tremor, Dystonia (humanitarian exemption), Obsessive- Compulsive disorder (humanitarian exemption) but not for focal hand dystonia.
Study population
Five adults with focal hand dystonia will be studied.
Design
This is a pilot study of 5 subjects with severe intractable FHD whose activities of daily living and quality of life are severely impaired. They will be recruited from our clinic and from referring practices. The subjects will undergo unilateral VOA/VOP DBS implantation, followed by programming to optimal parameters. The subjects will be followed at monthly intervals for 3 months, then every 3 months for 2 years, and then every 6 months until 5 years from the start. The safety of the procedure will be the primary outcome of the study. Trends toward efficacy will be assessed in several secondary outcomes, the most important ones being the change in dystonia severity and a quality of life scores. The electrophysiologic features of the motor ventral thalamic neurons will be recorded intraoperatively.
Outcome measures
Primary
-Number and severity of adverse events in the 5-year follow-up period.
Secondary
- Upper extremity sub-score of the Burke-Fahn-Marsden (BFM) scale and Arm Dystonia Disability Scale (ADDS) at baseline and every follow up visit
- For subjects with FHD type musician s dystonia: Tubiana and Chamagne scale at every follow up visit
- For subjects with FHD type Writer s cramp: Writer s Cramp Impairment Scale
- Improvement on patient reported outcomes evaluated by the SF-12 Health Status Survey at baseline and at every follow up visit
- Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery
- Dose of botulinum toxin injection required at baseline, 1 and 5 years.
Exploratory
- Intraoperatory electrophysiologic characteristics of the motor ventral thalamic neurons
- Local field potentials and their response to stimulation (in participants with implanted pulse generator capable of sensing capabilities)
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
- INCLUSION CRITERIA:
- FHD diagnosed by a neurologist
- BFM upper extremity subscore of 3 or more (score range 0 to 4) or ADDS difficulty of performing score equal to or more than 3.
- Patients must score 3 or below on the Tubiana and Chamagne scale or inability to perform at the concert level or patients must score a rating of "severe" on at least one item, impacting the patient s employment or essential activities on the Writer s Cramp Impairment scale.
- Symptoms causing significant impairment in quality of life and work or daily activities by patient self-assessment and SF12 scale, as reported by subjects. The subjects should be severely impaired in at least one of the following domains: handwriting, typing or playing an instrument. The impairment needs to have affected employment, manifested by substantive change in, or loss of, employment or career of choice.
- All patients must have failed or achieved inadequate benefit (continuing functional impairment) with at least two trials of botulinum toxin treatments.
- Women of childbearing age will have to agree to use contraception methods for the first 3 post operative months.
EXCLUSION CRITERIA:
- Subjects younger than 22 years old.
- MRI findings that would make participation and surgery unsafe (such as tumor or other space occupying lesion, stroke, hemorrhage or hematoma, edema, hydrocephalus, abscess) and MRI findings that would confound study outcomes (such as iron deposits in the basal ganglia, demyelinating disease, traumatic brain injury, structural or developmental abnormality, moderate or severe white matter hyperintensities).
- Subjects with prior brain surgery
- Pregnant or nursing women as safety of DBS has not been established in this group.
- Presence of a more widespread neurologic syndrome with the dystonia being part of it, and/or dystonia caused by an ongoing etiology, such as tardive dystonia associated with ongoing psychotropic treatment or an inherited neurodegenerative syndrome associated with intractable dystonia
- Intellectual disability as measured by the estimated General Ability Index (GAI) of the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), which would render the participant not able to provide informed consent or to comply with the study procedures (estimated GAI less than 70)
- Dementia as evidenced by formal neuropsychological evaluation and Mattis Dementia Rating Scale-2 (DRS-2) score below 128.
- Depressed subjects as determined by the neuropsychology or psychiatry screen, including Beck Depression Inventory (BDI) and psychiatric evaluation. Subjects scoring above 20 on the BDI or exhibiting moderate or severe active depression will be excluded
- Subjects with uncontrolled co-existing medical conditions: uncontrolled systemic hypertension with values above 170/100; active heart disease needing immediate intervention; active respiratory disease needing immediate intervention; uncorrected coagulation abnormalities; any condition that would render the patient unable to safely cooperate with the surgery and study tests as judged by the screening physician
Presence of a contraindication to undergo a brain MRI
- Metal in the body which would make having an MRI scan unsafe, such as pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner or small metal fragments in the eye that welders and other metal workers may have;
- Uncomfortable in small closed spaces (have claustrophobia) such that the participant will be uncomfortable in the MRI machine;
- Unable to lay comfortably flat on their back for up to one hour in the MRI scanner;
- Subjects who require diathermy
Subjects who require post-op MRIs with full body coil
-- Subjects with an active systematic infection
- Subjects who are immune-compromised
- Subjects who are on anticoagulation therapy that would preclude their ability to undergo the implant procedure
- Subjects who are allergic or have shown hypersensitivity to any materials of the neurostimulation system which may come in contact with the body
- Subjects that cannot appoint a Durable power of attorney (DPA)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active
single arm study
|
Unilateral thalamic DBS therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To confirm the safety of VOA/VOP thalamic DBS in FHD
Time Frame: 5 years
|
Number and severity of adverse events in the 5-year follow-up period.
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neuropsychological Evaluation
Time Frame: 5 years
|
To perform a neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery of the VOA/VOP complex in subjects with FHD
|
5 years
|
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in clinical improvement of severe intractable FHD
Time Frame: 5 years
|
Burke-Fahn-Marsden (BFM) scale and Arm Dystonia Disability Scale (ADDS) at baseline and every follow up visit
|
5 years
|
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improved patient reported outcomes
Time Frame: 5 years
|
Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery
|
5 years
|
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with musician s dystonia
Time Frame: 5 years
|
For subjects with FHD type Musician s Dystonia: Tubiana and Chamagne scale at every follow up visit
|
5 years
|
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with Writer s cramp
Time Frame: 5 years
|
For subjects with FHD type writer s cramp: Writer s Cramp Impairment Scale
|
5 years
|
To evaluate the botulinum toxin dose required for the treatment of FHD at baseline and 1 and 5 years after DBS therapy of the VOA/VOP complex
Time Frame: 5 years
|
Dose of Botulinum Toxin at 1 and 5 years
|
5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Debra J Ehrlich, M.D., National Institute of Neurological Disorders and Stroke (NINDS)
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 160166
- 16-N-0166
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Dystonia
-
University of Texas Southwestern Medical CenterMassachusetts General HospitalRecruitingDystonia | Dystonia; Idiopathic | Dystonia, Primary | Dystonia, Secondary | Dystonia, Familial | Dystonia Disorder | Dystonias, Sporadic | Dystonia; Orofacial | Dystonia Lenticularis | Dystonia, Paroxysmal | Dystonia 6 | Dystonia 5 | Dystonia 8 | Dystonia 9 | Dystonia 19 | Dystonia 10 | Dystonia 11 | Dystonia 20 | Dystonia 12 | Dystonia... and other conditionsUnited States
-
Fondation Ophtalmologique Adolphe de RothschildCompletedCervical Dystonia, PrimaryFrance
-
Duke UniversityAmerican Academy of NeurologyNot yet recruitingIsolated Focal Hand DystoniaUnited States
-
University Hospital, MontpellierTerminatedSpasticity | Isolated Cervical Dystonia | Complex DystoniaFrance
-
University of FloridaBachmann Strauss Dystonia & Parkinson Foundation, Inc.Completed
-
University Hospital, MontpellierTerminatedTardive Dystonia | Generalized Dystonia | Segmental DystoniaFrance
-
Institut National de la Santé Et de la Recherche...Assistance Publique - Hôpitaux de ParisNot yet recruiting
-
University of Colorado, DenverCompleted
-
National Institute of Neurological Disorders and...Completed
-
National Institute of Neurological Disorders and...CompletedOromandibular Dystonia | Cranial DystoniaUnited States
Clinical Trials on DBS surgery
-
St. Joseph's Hospital and Medical Center, PhoenixArizona State UniversityEnrolling by invitationParkinson DiseaseUnited States
-
National Institute of Neurological Disorders and...WithdrawnParkinson Disease
-
Oregon Health and Science UniversityCompleted
-
Deep Brain Innovations LLCTerminatedParkinson DiseaseUnited States
-
Chinese PLA General HospitalNot yet recruitingCervical DystoniaChina
-
St. Joseph's Hospital and Medical Center, PhoenixWithdrawnEssential TremorUnited States
-
St. Joseph's Hospital and Medical Center, PhoenixTerminatedParkinson's DiseaseUnited States
-
University Medical Center GroningenUnknown
-
University Hospital, BordeauxCompleted
-
Jaimie M. HendersonHarvard Medical School (HMS and HSDM); The Cleveland Clinic; Weill Medical College... and other collaboratorsCompletedTBI (Traumatic Brain Injury)United States