## Protocol Section
### Identification Module
**NCT ID:** NCT06422104

**Brief Title:** Neuromodulation Therapy for Task-Specific Dystonia

**Official Title:** Development of Mechanistically Informed Therapy for Task-Specific Dystonia Using Noninvasive Neuromodulation

#### Organization Study ID Info
**ID:** Pro00094131
#### Organization
**Class:** OTHER
**Full Name:** Duke University
### Status Module
#### Completion Date
**Date:** 2023-01-13

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-01-13

**Type:** ACTUAL

#### Start Date
**Date:** 2018-08-23

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-24
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Doris Duke Charitable Foundation

**Class:** OTHER

**Name:** Dystonia Coalition

**Class:** OTHER

**Name:** Dystonia Study Group

**Class:** NIH

**Name:** National Center for Advancing Translational Sciences (NCATS)

#### Lead Sponsor

**Class:** OTHER

**Name:** Duke University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 2-5

### Conditions Module

**Conditions:**

- Isolated Focal Hand Dystonia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** Double-blind cross-over design with participants receiving TMS at two cortical locations.

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** The TMS intensity and cortical location delivered at each TMS visit will be masked

**Who Masked:**

- PARTICIPANT

- OUTCOMES_ASSESSOR

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 12

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 10 Hz rTMS to premotor cortex

**Intervention Names:**

- Device: Repetitive transcranial magnetic stimulation

**Label:** 10 Hz rTMS to premotor cortex

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** 10 Hz rTMS to primary somatosensory cortex

**Intervention Names:**

- Device: Repetitive transcranial magnetic stimulation

**Label:** 10 Hz rTMS to primary somatosensory cortex

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** 0.7 Hz rTMS to premotor cortex

**Intervention Names:**

- Device: Repetitive transcranial magnetic stimulation

**Label:** 0.7 Hz rTMS to premotor cortex

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 0.7 Hz rTMS to premotor cortex

- 10 Hz rTMS to premotor cortex

- 10 Hz rTMS to primary somatosensory cortex

**Description:** 10 Hz repetitive TMS will be delivered for 20 minutes per session and 0.7 Hz for 20 minutes per session

**Name:** Repetitive transcranial magnetic stimulation

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Measure:** Feasibility of accurately delivering TMS during the task of writing as measured by number of participants who completed the TMS sessions

**Time Frame:** Visit 3 (week 1), Visit 4 (week 2), Visit 5 (week 3)

#### Secondary Outcomes

**Measure:** Safety, as measured by TMS acute side effects

**Time Frame:** Visit 3 (week 1), Visit 4 (week 2), Visit 5 (week 3)

**Description:** Using change in peak accelerations to assess writing behavior and further develop this writing behavior assessment tool throughout the study.

**Measure:** Feasibility, as measured by change in behavioral writing measure

**Time Frame:** Visit 3 (week 1), Visit 4 (week 2), Visit 5 (week 3)

**Description:** using functional magnetic resonance imaging of the brain

**Measure:** Change in brain connectivity in the motor network

**Time Frame:** Visit 3 (week 1), Visit 4 (week 2), Visit 5 (week 3)

### Eligibility Module

**Eligibility Criteria:** 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

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Durham

**Country:** United States

**Facility:** Duke University Health System

**State:** North Carolina

**Zip:** 27705

#### Overall Officials

**Official 1:**

**Affiliation:** Duke Health

**Name:** Noreen Bukhari-Parlakturk, MD PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Mulcahey PJ, Peterchev AV, Calakos N, Bukhari-Parlakturk N. Transcranial magnetic stimulation: the road to clinical therapy for dystonia. Dystonia. 2023 August; 2.

**Citation:** Bukhari-Parlakturk N, Mulcahey PJ, Lutz M, Ghazi R, Huang Z, Dannhauer M, Simsek Z, Groves S, Lipp M, Fei M, Tran T, Wood E, Beynel L, Scott B, Termsarasab P, Petty C, Al-Khalidi HR, Voyvodic J, Appelbaum LG, Davis S, Michael A, Peterchev AV, Calakos N. Functional MRI-guided personalized TMS decreases basal ganglia activity and improves focal hand dystonia. International Organization of Human Brain Mapping Conference. Montreal, Canada. July 22-26, 2023. virtual poster presentation.

**Citation:** Bukhari-Parlakturk N, Mulcahey PJ, Lutz M, Ghazi R, Huang Z, Dannhauer M, Simsek Z, Groves S, Lipp M, Fei M, Tran T, Wood E, Beynel L, Scott B, Termsarasab P, Petty C, Al-Khalidi HR, Voyvodic J, Appelbaum LG, Davis S, Michael A, Peterchev AV, Calakos N. Functional MRI-guided personalized TMS decreases basal ganglia activity and improves focal hand dystonia. International Dystonia Symposium. Dublin, Ireland. June 1-3, 2023. poster presentation.

**Citation:** Bukhari-Parlakturk N, Lutz MW, Al-Khalidi HR, Unnithan S, Wang JE, Scott B, Termsarasab P, Appelbaum LG, Calakos N. Suitability of Automated Writing Measures for Clinical Trial Outcome in Writer's Cramp. Mov Disord. 2023 Jan;38(1):123-132. doi: 10.1002/mds.29237. Epub 2022 Oct 13.

**PMID:** 36226903

**Citation:** Dannhauer M, Huang Z, Beynel L, Wood E, Bukhari-Parlakturk N, Peterchev AV. TAP: targeting and analysis pipeline for optimization and verification of coil placement in transcranial magnetic stimulation. J Neural Eng. 2022 Apr 21;19(2):10.1088/1741-2552/ac63a4. doi: 10.1088/1741-2552/ac63a4.

**PMID:** 35377345

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020820

- Term: Dyskinesias

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009069

- Term: Movement Disorders

- ID: D000002493

- Term: Central Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M7595

- Name: Dystonia

- Relevance: HIGH

- As Found: Dystonia

- ID: M22575

- Name: Dystonic Disorders

- Relevance: HIGH

- As Found: Dystonia

- ID: M22574

- Name: Dyskinesias

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12029

- Name: Movement Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2358

- Name: Focal Task-specific Dystonia

- Relevance: HIGH

- As Found: Task-Specific Dystonia

### Condition Browse Module - Meshes

- ID: D000004421

- Term: Dystonia

- ID: D000020821

- Term: Dystonic Disorders

### Misc Info Module

- Version Holder: 2024-05-31
