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| Name | Class |
|---|---|
| American Academy of Neurology | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sham TMS | Sham Comparator | Participants receive sham TMS |
|
| TMS to primary somatosensory cortex | Active Comparator | Participants received TMS sessions at primary somatosensory cortex |
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| TMS to primary somatosensory cortex (Open Label DBS Participants) | Active Comparator | Participants received TMS sessions at primary somatosensory cortex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Device | Participants will experience two accelerated transcranial magnetic stimulation (TMS) sessions, with 12 week (three-months) gap between each session. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (in person visit 4) |
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Inclusion Criteria for cervical dystonia subjects:
Exclusion Criteria for cervical dystonia subjects:
Inclusion criteria for cervical dystonia subjects considering DBS
Exclusion criteria for cervical dystonia subjects considering DBS
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| Name | Affiliation | Role |
|---|---|---|
| Noreen Bukhari-Parlakturk, MD PhD | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Health System | Durham | North Carolina | 27705 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 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." 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. | ||
| 36226903 |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D014282 | Trihexyphenidyl |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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Single-arm crossover study design with subjects receiving TMS at two different intensities
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The TMS intensity delivered at each TMS visit will be masked
| Placebo | Drug | Given 30 minutes before the TMS session. |
|
| trihexyphenidyl 10mg | Drug | Given 30 minutes before the TMS session. |
|
| 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 (in person visit 4) |
| 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. | 1 month, 3 month and 6-9 months |
| 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. |
| 35377345 | 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. |
| D006571 |
| Heterocyclic Compounds |