Deep Brain Stimulation Surgery for Focal Hand Dystonia
Primary Purpose
Dystonia, Focal Dystonia, Musician's Dystonia
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DBS surgery
Sponsored by
About this trial
This is an interventional treatment trial for Dystonia focused on measuring Electrophysiology, Neurosurgery, Dystonia, Deep Brain Stimulation
Eligibility Criteria
- 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 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 thepatient 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 anMRI 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)
Sites / Locations
- National Institutes of Health Clinical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Active
Arm Description
single arm study
Outcomes
Primary Outcome Measures
To confirm the safety of VOA/VOP thalamic DBS in FHD
Number and severity of adverse events in the 5-year follow-up period.
Secondary Outcome Measures
Neuropsychological Evaluation
To perform a neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery of the VOA/VOP complex in subjects with FHD
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in clinical improvement of severe intractable FHD
Burke-Fahn-Marsden (BFM) scale and Arm Dystonia Disability Scale (ADDS) at baseline and every follow up visit
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improved patient reported outcomes
Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with musician s dystonia
For subjects with FHD type Musician s Dystonia: Tubiana and Chamagne scale at every follow up visit
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with Writer s cramp
For subjects with FHD type writer s cramp: Writer s Cramp Impairment Scale
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
Dose of Botulinum Toxin at 1 and 5 years
Full Information
NCT ID
NCT02911103
First Posted
September 21, 2016
Last Updated
April 27, 2023
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT02911103
Brief Title
Deep Brain Stimulation Surgery for Focal Hand Dystonia
Official Title
Deep Brain Stimulation Surgery for Treatment of Focal Hand Dystonia
Study Type
Interventional
2. Study Status
Record Verification Date
February 28, 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 17, 2018 (Actual)
Primary Completion Date
February 2, 2029 (Anticipated)
Study Completion Date
February 2, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
5. Study Description
Brief Summary
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.
...
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
Intraoperatory electrophysiologic characteristics of the motor ventral thalamic neurons
Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery
Dose of botulinum toxin injection required at baseline, 1 and 5 years.
Exploratory
-Local field potentials and their response to stimulation (in participants with implanted pulse generator capable of sensing capabilities)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dystonia, Focal Dystonia, Musician's Dystonia
Keywords
Electrophysiology, Neurosurgery, Dystonia, Deep Brain Stimulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active
Arm Type
Experimental
Arm Description
single arm study
Intervention Type
Procedure
Intervention Name(s)
DBS surgery
Intervention Description
Unilateral thalamic DBS therapy
Primary Outcome Measure Information:
Title
To confirm the safety of VOA/VOP thalamic DBS in FHD
Description
Number and severity of adverse events in the 5-year follow-up period.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Neuropsychological Evaluation
Description
To perform a neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery of the VOA/VOP complex in subjects with FHD
Time Frame
5 years
Title
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in clinical improvement of severe intractable FHD
Description
Burke-Fahn-Marsden (BFM) scale and Arm Dystonia Disability Scale (ADDS) at baseline and every follow up visit
Time Frame
5 years
Title
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improved patient reported outcomes
Description
Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery
Time Frame
5 years
Title
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with musician s dystonia
Description
For subjects with FHD type Musician s Dystonia: Tubiana and Chamagne scale at every follow up visit
Time Frame
5 years
Title
To determine if thalamic DBS targeting the VOA/VOP nuclear complex results in improvement of severe intractable FHD in subjects with Writer s cramp
Description
For subjects with FHD type writer s cramp: Writer s Cramp Impairment Scale
Time Frame
5 years
Title
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
Description
Dose of Botulinum Toxin at 1 and 5 years
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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 thepatient 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 anMRI 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Irene H Dustin, C.R.N.P.
Phone
(301) 402-4479
Email
irene.dustin@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Debra J Ehrlich, M.D.
Phone
(301) 443-7888
Email
debra.ehrlich@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Debra J Ehrlich, M.D.
Organizational Affiliation
National Institute of Neurological Disorders and Stroke (NINDS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY8664111010
Email
prpl@cc.nih.gov
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
.It has not been determined whether sharing IPD will be feasible for this study.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2016-N-0166.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Deep Brain Stimulation Surgery for Focal Hand Dystonia
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