Accelerating TMS for Cervical Dystonia

NCT06328114 | Enrolling By Invitation Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: Pro00114549
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the impact of accelerated transcranial magnetic stimulation (TMS) on brain function and behavior in patients with focal cervical dystonia. Previous research demonstrated that individualized TMS improved writing behavior in focal hand dystonia after one session. In this study, we aim to expand the application on TMS on focal cervical dystonia. The current study administers six sessions of TMS separated by five rest blocks, all in a single day and combined with a medication called trihexyphenidyl given 30 minutes before the TMS session. This approach is called "anticholinergic enhanced accelerated TMS The research involves 8 in-person visits and 3 remote visits over 28 weeks. The effect of TMS will be assessed using functional MRI brain scans and behavioral measurements. Participants who are interested in enrolling in the TMS study to assess their potential presurgical response to DBS will only receive the active TMS session combined with trihexyphenidyl medication. After active TMS + trihexyphenidyl medication, participants will be followed for 3-5months to assess their brain and behavior response to TMS. Following clinical care DBS, participants will be followed for three additional research visits. The three visits will be performed at 1 month, 3 months and 6-9 months. During the post-DBS research visits, participants will complete behavioral assay and physiological assay to evaluate their neck movements and muscles. At 3 month or 6-9 month visit, the post-DBS participants will also undergo fMRI with the DBS device in off mode setting. The risk of TMS includes seizures; the potential risk of seizures from TMS is mitigated through careful screening, adhering to safety guidelines. The study's main benefit is enhancing dystonic behavior and deepening the understanding of brain changes caused by TMS in cervical dystonia, paving the way for further advancements in clinical therapy for this condition.

Conditions

Isolated Cervical Dystonia

Outcome Measures

Primary Outcomes (1)

• Change in Neck Angles as Measured by Neck Sensor Device

  Mixed modeling will be used to compare the degree of neck angle movements between active TMS, sham TMS, and baseline visits.

  Baseline, approximately 24 weeks (in person visit 8)

Secondary Outcomes (3)

• Changes in Brain Activity (bold activity) on Functional Magnetic Resonance Imaging (fMRI)

  Baseline (visit 1) to approximately 4 weeks (in person visit 4)

• Changes in Brain Activity (functional connectivity) on Functional Magnetic Resonance Imaging (fMRI)

  Baseline (visit 1) to approximately 4 weeks (in person visit 4)

• Behavioral Response After Deep Brain Stimulation (DBS), as measured by Neck Angles

  1 month, 3 month and 6-9 months

Study Arms (3)

sham TMS

SHAM COMPARATOR

Participants receive sham TMS

Device: Transcranial Magnetic Stimulation (TMS); Drug: Placebo

TMS to primary somatosensory cortex

ACTIVE COMPARATOR

Participants received TMS sessions at primary somatosensory cortex

Device: Transcranial Magnetic Stimulation (TMS); Drug: trihexyphenidyl 10mg

TMS to primary somatosensory cortex (Open Label DBS Participants)

ACTIVE COMPARATOR

Participants received TMS sessions at primary somatosensory cortex

Drug: trihexyphenidyl 10mg

Interventions

Placebo DRUG

Given 30 minutes before the TMS session.

sham TMS

trihexyphenidyl 10mg DRUG

Given 30 minutes before the TMS session.

TMS to primary somatosensory cortex; TMS to primary somatosensory cortex (Open Label DBS Participants)

Transcranial Magnetic Stimulation (TMS) DEVICE

Participants will experience two accelerated transcranial magnetic stimulation (TMS) sessions, with 12 week (three-months) gap between each session.

TMS to primary somatosensory cortex; sham TMS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• yrs and older
• Diagnosed with isolated cervical dystonia by Neurologist
• Must be able to sign an informed consent
• Must be literate

You may not qualify if:

• Other neurological movement disorders diagnoses including other types of dystonia, Parkinsonism, or essential tremor
• History of seizure disorder
• Concomitant medications known to decrease seizure threshold
• Illicit drug use
• No TMS therapy for another indication within one month of this research study
• Botulinum toxin injections within 3 months of the research study
• Medications used for symptom treatment of dystonia including anticholinergic, benzodiazepines, and muscle relaxants among others within one month of the study
• No physical or occupational therapy of the neck within one month of the study
• Any contraindications to MRI or TMS
• yrs and older
• diagnosed with cervical dystonia by a Neurologist
• must be able to sign informed consent
• must be literate
• On no medications or one medication to treat symptoms of dystonia for a minimum of one month prior to study participation
• other neurological movement disorders diagnoses including Parkinsonism, or essential tremor

Sponsors & Collaborators

• Duke University: lead
• American Academy of Neurology: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27705, United States

Location

Related Publications (4)

• Noreen Bukhari-Parlakturk, Patrick Mulcahey, Michael Lutz, Rabia Ghazi, Ziping Huang, Moritz Dannhauer, Zeynep Simsek, Skylar Groves, Mikaela Lipp, Michael Fei, Tiffany Tran, Eleanor Wood, Lysianne Beynel, Burton Scott, Pichet Termsarasab, Chris Petty, Hussein R Al-Khalidi, James Voyvodic, Lawrence G. Appelbaum, Simon Davis, Andrew Michael, Angel Peterchev, Nicole Calakos. "Functional MRI-guided individualized TMS modifies motor network and reduces writing dysfluency in Focal Hand Dystonia." Human Brain Mapping Conference. Montreal, Canada. July 22-26, 2023. virtual poster presentation.

  BACKGROUND

• Noreen Bukhari-Parlakturk, Patrick Mulcahey, Michael Lutz, Rabia Ghazi, Ziping Huang, Moritz Dannhauer, Zeynep Simsek, Skylar Groves, Mikaela Lipp, Michael Fei, Tiffany Tran, Eleanor Wood, Lysianne Beynel, Burton Scott, Pichet Termsarasab, Chris Petty, Hussein R Al-Khalidi, James Voyvodic, Lawrence G. Appelbaum, Simon Davis, Andrew Michael, Angel Peterchev, Nicole Calakos. "Functional MRI-guided individualized TMS modifies motor network and reduces writing dysfluency in Focal Hand Dystonia." Samuel Belzberg 6th International Dystonia Symposium. Dublin, Ireland. June 1-3, 2023. poster presentation.

  BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Interventions

Transcranial Magnetic Stimulation; Trihexyphenidyl

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Noreen Bukhari-Parlakturk, MD PhD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The TMS intensity delivered at each TMS visit will be masked
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm crossover study design with subjects receiving TMS at two different intensities

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 25, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)