Clinical trial NCT06328114: Accelerating TMS for Cervical Dystonia
Official title: Functional Magnetic Resonance Imaging (fMRI)-Guided Individualized Transcranial Magnetic Stimulation (TMS) for Cervical Dystonia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Isolated Cervical Dystonia
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: American Academy of Neurology
First posted: 2024-03-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-arm crossover study design with subjects receiving TMS at two different intensities
Primary purpose: TREATMENT

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 four TMS sessions in a day. The research involves 9 in-person visits. The effect of TMS will be assessed using functional MRI brain scans and behavioral measurements. 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.

Detailed description: The primary aim of this research is to investigate the impact of transcranial magnetic stimulation (TMS) on both brain function and behavioral outcomes among individuals with cervical dystonia. A previous TMS study carried out by our team revealed that the application of TMS using a personalized brain targeting approach in focal hand dystonia resulted in improved measures of writing disfluency and changes in the motor network. This study seeks to expand these promising findings to individuals with cervical dystonia. Subjects in the study will receive four TMS sessions in a single day with a protocol referred to as "accelerated TMS." The investigation will consist of a total of 9 in-person appointments. Participants with cervical dystonia will receive accelerated TMS during two in-person visits. Following each TMS session, participants will evaluate changes in brain function using function MRI and behavior using a behavior assay. The principal risk associated with TMS is the possibility of inducing a seizure. However, this study will strictly adhere to safety guidelines, utilizing TMS levels that have not previously been linked to seizures in properly screened individuals. The dosages of TMS proposed for use in this study have not caused seizures in healthy volunteers. To further mitigate the risk of seizures, potential subjects will undergo medical screening for any known factors that could predispose them to seizures. The primary advantage of this study is that it may improve neck movement behavior in patients with cervical dystonia, while also advancing our understanding in brain function before and after TMS intervention. The discoveries stemming from this investigation will pave the way for future research endeavors aimed at advancing brain stimulation as a viable clinical therapy for cervical dystonia.

Eligibility criteria: Inclusion Criteria:

* 18yrs and older
* Diagnosed with isolated cervical dystonia by Neurologist
* Must be able to sign an informed consent
* Must be literate

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in Neck Angles as Measured by Neck Sensor Device
timeFrame: Baseline, approximately 7 months (visit 9)
Secondary outcomes:
measure: Changes in Brain Activity (bold activity) on Functional Magnetic Resonance Imaging (fMRI)
timeFrame: Baseline (visit 1) to approximately 4 weeks (visit 7)
measure: Changes in Brain Activity (functional connectivity) on Functional Magnetic Resonance Imaging (fMRI)
timeFrame: Baseline (visit 1) to approximately 4 weeks (visit 7)
measure: Behavioral Response After Deep Brain Stimulation (DBS), as measured by Neck Angles
timeFrame: Approximately 6 weeks post-DBS (visit 8), approximately 7 months (visit 9)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Noreen Bukhari-Parlakturk, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.
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.