Non-invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in Functional Movement Disorders
Phase II Trial of Non-Invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in Functional Movement Disorders
Background:
Functional movement disorders (FMD) involve involuntary movements that are not due to a recognized neurological or medical cause. FMD can cause major disability. Researchers want to learn more to create better treatments for FMD.
Objective:
To test whether non-invasive brain stimulation using transcranial magnetic stimulation (TMS) improves FMD symptoms.
Eligibility:
People between the ages of 18 and 80 who have been diagnosed with FMD by a neurologist.
Design:
Participants will be randomly assigned to one of two groups. One group is an active brain stimulation group and the other is a sham brain stimulation group.
Participants will have a baseline visit. This will include:
Neurological exam
Questionnaires
Urine test
Brain MRI: Participants will lie in a machine that takes pictures of the body. They will be asked to respond to images on a screen while in the scanner.
Within 2 weeks of the baseline visit, participants will begin 5 daily sessions of TMS. The active group will have stimulation delivered to the brain via a coil. In the sham group, a dummy coil will be used that will not deliver stimulation. A total of three 3-minute cycles will be done in one visit. There will be 20-minute breaks between the cycles.
Participants will have visits 1 month, 2 months, and 6 months after their last day of TMS. Their FMD symptoms will be evaluated. They will complete health questionnaires. These visits can be in person or virtual.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Description:
The purpose of this protocol is to investigate efficacy of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) in patients with functional movement disorders (FMD). Participants will be randomly assigned to receive either active iTBS or sham stimulation of the left DLPFC for 5 consecutive daily sessions.
Objectives:
Primary Objective: To investigate efficacy of iTBS of the left DLPFC on motor symptoms in patients with FMD
Secondary Objectives: To investigate efficacy of iTBS of the left DLPFC on mood symptoms and its effect on fronto-amygdala circuit on functional neuroimaging
Endpoints:
Primary Endpoint: Relative change in Functional Movement Disorder Rating Scale (S-FMDRS) from the baseline to 1 month after iTBS vs sham: 100 *( S-FMDRS at one-month - S-FMDRS at baseline)/ S-FMDRS at baseline
Secondary Endpoints:
- S-FMDRS immediately after, 2 months and 6 months after the treatment
- HADS at 1 month, 2 months and 6 months after the treatment
- DLPFC-amygdala functional connectivity
- Amygdala BOLD response to emotional stimuli
Study Type
Enrollment (Actual)
Phase
- Not Applicable
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:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 18-80
- Diagnosis of functional movement disorder made by a neurologist
- Agreement to adhere to Lifestyle Considerations throughout study duration
- Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- Current psychosis or active suicidal ideation
- History of epilepsy with the exception of febrile seizure
- Patients with psychogenic non-epileptic seizure without comcomitant functional movement disorder
- Any significant neurological disorders other than FMD including but not limited to multiple sclerosis, stroke, Parkinson s disease, space occupying brain lesion
- Alcohol or substance use disorder
- Patients who are on Buproprion (Wellbutrin)
- Patients with moderate to severe cardiac disease
- Any psychiatric, medical or social condition due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient.
- Pregnancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Sham Comparator: Control
Sham TMS stimulation using a sham coil
|
Sham TMS stimulation using a sham coil
|
|
Experimental: Treatment
Active TMS stimulation using an active TMS coil
|
Bursts of three at 50Hz with an inter burst interval of 200 ms will be given for 190 seconds and this session will be repeated 3 times with 20 minutes between each session in one day.
The set of 3 sessions will be repeated 5 times in 5 consecutive days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in S-FMDRS at 1 Month After Real iTBS vs Sham iTBS
Time Frame: 1 month after iTBS
|
The Simplified Functional Movement Disorders Rating Scale (S-FMDRS) measures abnormal movements in 7 body regions as well as gait and speech.
Symptom severity in each body region is rated from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe) and duration from 0 to 3 (0=none; 1=occasionally, 2=frequent, 3= constant).
All severity and duration scores are added to yield a total score.
The total score ranges from minimum 0 to maximum 68, high score representing worse outcome.
|
1 month after iTBS
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in S-FMDRS at 2 and 6 Months After Real iTBS vs Sham iTBS
Time Frame: 2 and 6 months after iTBS
|
The Simplified Functional Movement Disorders Rating Scale (S-FMDRS) measures abnormal movements in 7 body regions as well as gait and speech.
Symptom severity in each body region is rated from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe) and duration from 0 to 3 (0=none; 1=occasionally, 2=frequent, 3= constant).
All severity and duration scores are added to yield a total score.
The total score ranges from minimum 0 to maximum 68, high score representing worse outcome.
|
2 and 6 months after iTBS
|
|
Change in Hospital Anxiety and Depression Scale (HADS) at 1, 2 and 6 Months After Real iTBS vs Sham iTBS
Time Frame: At baseline and 1, 2 and 6 months after iTBS
|
Hospital Anxiety and Depression Scale (HADS) is a continuous numeric scale in depression and anxiety (depression 0-21 and anxiety 0-21, higher score representing worse outcome) and the questions ask about the feeling in the past week.
This was repeatedly measured at baseline, then at 1 month, 2 months and 6 months after iTBS vs sham and was compared between iTBS vs sham group.
|
At baseline and 1, 2 and 6 months after iTBS
|
|
CGI at 1, 2, and 6 Months After Real iTBS vs Sham iTBS
Time Frame: 1, 2 and 6 months after iTBS
|
The Clinical Global Impression (CGI) can assess patient's view of the patient's global functioning prior to and after initiating a study medication.
The CGI scale of 1-7 is a measure of clinical improvement from the intervention, higher score presenting worse outcome.
(1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse)
|
1, 2 and 6 months after iTBS
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in SF-36 at 1, 2, and 6 Months After Real iTBS vs Sham iTBS
Time Frame: Baseline and at 1, 2 and 6 months after iTBS
|
The short form (36) health survey is an indicator of health-related quality of life using 36 questions. It has eight domains; the scores are weighted sums of the questions in each domain. Scores range from 0 - 100 in each domain (lower scores = more disability, higher scores = less disability).
|
Baseline and at 1, 2 and 6 months after iTBS
|
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 (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10000642
- 000642-N
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
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.