Accelerating TMS for Cervical Dystonia

Официальное название

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

Обзор

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.

Подробное описание

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 8 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.

Вмешательства

• Устройство Transcranial Magnetic Stimulation (TMS)
  Participants will experience two accelerated transcranial magnetic stimulation (TMS) sessions, with 12 week (three-months) gap between each session.
• Препарат Placebo
  Given 30 minutes before the TMS session.
• Препарат trihexyphenidyl 10mg
  Given 30 minutes before the TMS session.

Первичные конечные точки

• Change in Neck Angles as Measured by Neck Sensor Device [Срок оценки: Baseline, approximately 24 weeks (in person visit 8)]

Вторичные конечные точки (3)

• Changes in Brain Activity (bold activity) on Functional Magnetic Resonance Imaging (fMRI) [Срок оценки: Baseline (visit 1) to approximately 4 weeks (in person visit 4)]
• Changes in Brain Activity (functional connectivity) on Functional Magnetic Resonance Imaging (fMRI) [Срок оценки: Baseline (visit 1) to approximately 4 weeks (in person visit 4)]
• Behavioral Response After Deep Brain Stimulation (DBS), as measured by Neck Angles [Срок оценки: 1 month, 3 month and 6-9 months]

Критерии участия

Inclusion Criteria for cervical dystonia subjects:

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

Exclusion Criteria for cervical dystonia subjects:

• 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

Inclusion criteria for cervical dystonia subjects considering DBS

• 18yrs 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

Exclusion criteria for cervical dystonia subjects considering DBS

• other neurological movement disorders diagnoses including Parkinsonism, or essential tremor
• botulinum toxin injections within 3 months of research study
• More than two medications used for symptom treatment of dystonia including anticholinergic, benzodiazepines, and muscle relaxants among others within one month of the study
• contraindications to MRI or TMS
• a history of seizures and anti-seizure medications by review of medical records

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Duke University Health System — Durham

Публикации

• 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 i
• 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 i
• 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
• 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

Идентификаторы

NCT: NCT06328114 · Pro00114549

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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