Isolated Focal Hand Dystonia
Conditions
Brief summary
This study aims to apply a non-invasive brain stimulation technology called repetitive Transcranial Magnetic Stimulation (rTMS) in patients with focal hand dystonia (FHD). The goal of the study is to identify which cortical target (premotor cortex (PMC) or primary somatosensory cortex (PSC)) will show benefit after active rTMS compared to sham rTMS. A secondary goal of the study is to understand if 10 Hz rTMS can show behavioral benefit compared to sham rTMS. The study will evaluate rTMS response using measures if writing on a sensor tablet, examiner and patient dystonia rating scales and brain imaging scan (functional MRI) to understand brain changes after rTMS. Safety measures include adherence to TMS guidelines and thorough medical screening to prevent seizures.
Detailed description
The primary objective of this study is to develop rTMS for FHD. The focus is to assess whether stimulating the PMC or PSC will show greater improvement in writing behavior. This research builds upon prior studies that have demonstrated improvement in behavior after rTMS to PMC and PSC. The study includes five sequential visits: * Visit 1 behavior writing measures and dystonia rating scales. * Visit 2 includes task-based functional MRI brain scans to develop cortical target for rTMS sessions. * Visits 3, 4, and 5: FHD participants receive 10 Hz rTMS to PMC, PSC and sham rTMS to PMC in a cross over design with at minimum one week of washout between sessions. Participants complete behavior writing measures and rating scales on same day before and after each TMS session and an fMRI after each TMS session. Up to 5 Healthy Volunteers were recruited to help develop the TMS visits. The information in this record reflects Visits 3-5
Interventions
DEVICERepetitive transcranial magnetic stimulation
10 Hz repetitive TMS will be delivered for 20 minutes per session and 0.7 Hz for 20 minutes per session
Sponsors
Duke University
Doris Duke Charitable Foundation
Dystonia Coalition
Dystonia Study Group
National Center for Advancing Translational Sciences (NCATS)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The TMS intensity and cortical location delivered at each TMS visit will be masked
Intervention model description
Double-blind cross-over design with participants receiving TMS at two cortical locations.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy Control Participants: 1. 18yrs and older 2. Left or Right hand dominance 3. Age-matched to Focal Hand dystonia patients 4. Must be able to sign informed consent 5. Must be literate * Focal Hand dystonia Patients: 1. 18yrs and older 2. Left or Right hand dominance 3. Diagnosed with Writer's Cramp dystonia in left or right hand 4. Must be able to sign informed consent 5. Must be literate
Exclusion criteria
Healthy Control Participants (visits 2, 3, 4, and 5) and Focal Hand dystonia Patients (visits 2, 3, 4, and 5): 1. Other neurological movement disorders diagnoses including other types of dystonia, Parkinsonism, or essential tremor 2. Botulinum toxin injections within 3 months of research study 3. Medications with effects on the central nervous system including anticholinergic, benzodiazepines, and muscle relaxants among others within 1 week of the study 4. No physical or occupational therapy of the upper extremities 5. Any contraindications to MRI (ie: metal in body or implanted medical devices, etc) 6. Any contraindication on TMS adult safety screening (TASS form) including seizure history, pregnancy, brain injury, cranial metal implants, known structural brain lesion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of Accurately Delivering TMS During the Task of Writing as Measured by Number of Participants Who Completed the TMS Sessions | Pre-TMS and post-TMS session (each session is approximately 45 minutes) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety, as Measured by TMS Acute Side Effects | During TMS session (each session is approximately 45 minutes) | — |
| Change in Peak Accelerations Behavior (Calculated by Taking the Change in Peak Accelerations From Behavior Performed Before and After Each TMS Visit). | Pre-TMS and post-TMS session (each session is approximately 45 minutes) | Change in peak accelerations behaviors pre- and post-TMS is calculated by taking the change in peak accelerations from behavior performed before and after each TMS visit. Higher measures of peak accelerations represent greater writing dysfluency and worsening dystonia. |
| Brain Connectivity Between Superior Parietal Cortex to Right Cerebellum VIII | Post-TMS session (each session is approximately 45 minutes) | Brain connectivity was assessed using functional magnetic resonance imaging of the brain. The z-score is mathematical calculation of the synchronization between brain regions. Specifically, functional connectivity z-scores quantify the strength of synchronization between brain regions by transforming Pearson correlation coefficients (r-values) into normally distributed values (z-scores). This Fisher-z transformation stabilizes variance, enabling valid group-level statistical comparisons (e.g., t-tests) of functional connectivity. Positive Z-scores (Z scores\> 0) represent stronger synchronization between brain regions and strengthening of connectivity between brain regions; negative Z-scores (Z-scores \<0) indicate anti-synchronization between brain regions and weakening of connectivity between brain regions. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNoreen Bukhari-Parlakturk, MD PhD
Duke Health
Participant flow
Pre-assignment details
The study was a cross-over design with multiple visits and measures to compare differences in data within participants across the three TMS conditions. Healthy volunteers were not enrolled in the trial represented in this results submission.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
None listed