Functional Magnetic Resonance Imaging (fMRI)-Guided Individualized Transcranial Magnetic Stimulation (TMS) for Cervical Dystonia
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Neck Angles as Measured by Neck Sensor Device
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The TMS intensity delivered at each TMS visit will be masked
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
sham TMS
Participants receive sham TMS
干预措施: Transcranial Magnetic Stimulation (TMS) (Device)
TMS to primary somatosensory cortex
Participants received TMS sessions at primary somatosensory cortex
干预措施: Transcranial Magnetic Stimulation (TMS) (Device)
sham TMS
Participants receive sham TMS
干预措施: Placebo (Drug)
TMS to primary somatosensory cortex
Participants received TMS sessions at primary somatosensory cortex
干预措施: trihexyphenidyl 10mg (Drug)
TMS to primary somatosensory cortex (Open Label DBS Participants)
Participants received TMS sessions at primary somatosensory cortex
干预措施: trihexyphenidyl 10mg (Drug)
结局指标
主要结局
Change in Neck Angles as Measured by Neck Sensor Device
时间窗: Baseline, approximately 24 weeks (in person visit 8)
Mixed modeling will be used to compare the degree of neck angle movements between active TMS, sham TMS, and baseline visits.
次要结局
- 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)