Accelerating TMS for Cervical Dystonia

Isolated Cervical Dystonia Clinical Trial

Official title:

Functional Magnetic Resonance Imaging (fMRI)-Guided Individualized Transcranial Magnetic Stimulation (TMS) for Cervical Dystonia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06328114
• Other study ID #: Pro00114549
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: July 1, 2029

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: Noreen Bukhari-Parlakturk, MD PhD
• Phone: (919) 668-8248
• Email: movdisres[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: July 1, 2029
• Est. primary completion date: July 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders
• Isolated Cervical Dystonia
• Torticollis

Intervention

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

Locations

Country	Name	City	State
United States	Duke University Health System	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	American Academy of Neurology

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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.

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 7 months (visit 9)
Secondary	Changes in Brain Activity (bold activity) on Functional Magnetic Resonance Imaging (fMRI)	The investigators will conduct a region of interest analysis in the motor network of the brain to calculate changes of fMRI bold activity after each TMS session.	Baseline (visit 1) to approximately 4 weeks (visit 7)
Secondary	Changes in Brain Activity (functional connectivity) on Functional Magnetic Resonance Imaging (fMRI)	The investigators will conduct a region of interest analysis in the motor network of the brain to calculate changes of fMRI functional connectivity after each TMS session.	Baseline (visit 1) to approximately 4 weeks (visit 7)
Secondary	Behavioral Response After Deep Brain Stimulation (DBS), as measured by Neck Angles	If participants undergo DBS, the investigators will collect neck angles over time post-DBS and correlate with the subject's neck angles over time post-TMS.	Approximately 6 weeks post-DBS (visit 8), approximately 7 months (visit 9)