The Effect of Noninvasive Brain Stimulation on Symptoms of Cervical Dystonia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Symptoms of cervical dystonia - TWSTRS total score
研究概览
简要总结
The primary aim of this study is to assess whether continuous theta-burst stimulation (cTBS) can be helpful in reducing symptoms of idiopathic cervical dystonia. This will be a parallel-group, randomised, sham-controlled, double blind clinical trial. Patients and investigators measuring patient symptoms clinical scales will be blinded from allocation group, investigators delivering the intervention will not be blinded, as this is not feasible. Real cTBS will be compared to sham cTBS, with patients allocated to these two groups with a 1:1 recruitment ratio.
Bilateral cTBS will be delivered four times daily, over eight days, for a total of 32 bilateral cTBS sessions. The primary outcome is the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). This will be administered at T1 (pre-cTBS), T2 (day 10, following days 2-9 where patients received the intervention), T3 (2 weeks post the final session of cTBS), and T4 (4-5 weeks post the final session of cTBS).
Secondary outcomes will be the TWSTRS subscales (severity, disability, pain), Quality of Life scale, Global dystonia severity rating scale (GDS), Fahn Tolosa Marin (FTM) modified (to include only questions relevant to head/neck tremor) tremor scale, kinematic data of patient's movement patterns, motor evoked potentials (MEPs), and resting-state fMRI data (fMRI).
详细描述
Cervical dystonia (CD) is the most common form of dystonia and is characterised by excessive and involuntary muscle contractions of the muscles in the neck. Whilst botulinum neurotoxin (BoNT) injections to the affected muscles can provide therapeutic relief to CD patients, up to one-third of patients report an inadequate response to treatment. In more severe cases, deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus is an effective treatment for CD symptoms, directly and indirectly modulating networks thought to be abnormal in CD. TMS trials have previously been conducted to investigate its potential to ameliorate CD symptoms. These studies have shown limited success, with small sample sizes, and variable results. A major factor limiting the more effective use of TMS in CD is that it is not yet known where to target with TMS, given the many structures implicated in the neurobiology of the disorder. A prior study using lesion network mapping in CD attempted to address this issue by localising a brain network connected to lesions causing CD. Corp, et al. demonstrated that although causal lesions were located throughout the brain, all lesions were functionally connected to a brain network involving positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex (S1). Preliminary work from our group examined the effect of targeting this lesion network mapping-derived S1 cluster using TMS. First, a single session of continuous theta-burst stimulation (cTBS) to the S1 indicated target engagement, as demonstrated by abnormal metabolic response in CD patients, and next, a pilot trial of 10 days of daily cTBS demonstrated a 12% reduction in CD symptoms. The primary aim of this study is to assess whether a higher-dose of (4x daily) cTBS can increase therapeutic effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participants and outcome assessors are blinded to treatment allocation. The investigators administering cTBS are not blinded due to the nature of the intervention but are not involved in outcome assessments.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and 85 years
- •Diagnosis of idiopathic cervical dystonia made by an expert physician
- •Last botulinum toxin injection administered at least two months before the start of participation in the study (Albanese, Abbruzzese et al. 2015)
排除标准
- •Head or neck trauma occurring less than 12 months before the onset of dystonia
- •Acquired dystonia (e.g., drug-induced, brain lesions or trauma)
- •History of major psychiatric disorders (e.g., bipolar disorder, schizophrenia, obsessive-compulsive disorder)
- •History of neurological diseases other than CD (e.g., epilepsy, Parkinson's disease)
- •Other contraindications for TMS or brain MRI (e.g., metal in the head)
- •Pregnant or breastfeeding women
- •History of substance abuse or dependence
结局指标
主要结局
Symptoms of cervical dystonia - TWSTRS total score
时间窗: For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
The total score on the Toronto Western Spasmodic Torticollis Rating Scale
次要结局
- Symptoms of cervical dystonia - TWSTRS subscales(For a single patient, a minimum of 6 weeks and a maximum of 16 weeks)
- Symptoms of cervical dystonia - kinematic recordings(For a single patient, 10 days. Pre and post cTBS)
- Motor evoked potentials(For a single patient, 10 days. Pre and post cTBS)
- Magnetic resonance imaging(For a single patient, 10 days. Pre and post cTBS)
- Fahn Tolosa Marin tremor scale(For a single patient, a minimum of 6 weeks and a maximum of 16 weeks)
- Global dystonia severity rating scale(For a single patient, a minimum of 6 weeks and a maximum of 16 weeks)