RTMS for Adults with Severe Tourette Syndrome

针对成人严重抽动秽语综合征的 RTMS

• 批准号: 7568946
• 负责人: JAMES F LECKMAN
• 金额: $ 18.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7568946
• 关键词: Adult; Adverse effects; Affect; Area; Attention deficit hyperactivity disorder; Bilateral; Brain; Chronic; Clinical; Data; Disease; Disease remission; Double-Blind Method; Etiology; Feasibility Studies; Gilles de la Tourette syndrome; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Measures; Mink; Monitor; Motor; Motor Cortex; Obsessive-Compulsive Disorder; Outcome; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Physiologic pulse; Population; Randomized; Randomized Clinical Trials; Relapse; Relative (related person); Reporting; Safety; Sampling; Screening procedure; Severities; Site; Symptoms; Therapeutic; Tic disorder; Transcranial magnetic stimulation; blind; clinical care; clinically significant; depression; depressive symptoms; design; disability; efficacy testing; experience; improved; intervention effect; neuropsychiatry; repetitive transcranial magnetic stimulation; success

DESCRIPTION (provided by applicant): Tourette syndrome (TS) and related neuropsychiatric conditions affect as many as 0.3 -1% of the population. They are chronic, relapsing disorders that can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond to the available treatments or experience intolerable side effects. Most of the widely used interventions result in at best a 30 to 40% reduction in tic severity. Although the etiology of TS is unknown, emerging knowledge concerning the underlying neurocircuitry has been used to guide the design of focal brain stimulation strategies to study and treat tic disorders. Transcranial magnetic stimulation (TMS) has been used to investigate TS for the past decade and repetitive TMS (rTMS) has been used as an investigational intervention for severe TS for at least the last five years. Initial rTMS studies targeting motor and premotor cortical sites with either 1 Hz or 15 Hz have had limited or no success in treating individuals with severe TS. However, the recent study by Mantovani et al. (2006) which targeted the Supplementary Motor Area (SMA) was the first to demonstrate that 1 Hz rTMS produced clinically significant improvement (67% reduction in tic severity) in five patients with TS. Two of these patients experienced a complete remission of their tic symptoms. These improvements were maintained for three months. This was an open study in which patients were treated five days a week for two weeks, for a total of 10 treatments. No major side effects were noted during the course of treatment or the subsequent three months. This Phase II clinical trial proposes to replicate the Mantovani et al. (2006) study using a sham stimulation control condition. We anticipate screening 50 patients and selecting 30 patients to participate in a randomized clinical trial (15 randomized to sham and 15 to active rTMS). Two sites will administer rTMS, Yale and Columbia. We will monitor the effects of these interventions using a blind, independent evaluator. This pilot/feasibility study will allow us to make accurate power estimates for a subsequent R01 to test the efficacy and side effects of rTMS to the SMA in a larger sample, and to examine side effects, secondary electrophysiological outcomes (paired-pulse TMS to measure the excitability of the motor cortex), secondary clinical outcomes (obsessive-compulsive symptoms, depressive symptoms, and attention deficit hyperactivity disorder symptoms), and the relative impact of concurrently administered medications.

描述（由申请人提供）：抽动秽语综合症 (TS) 和相关的神经精神疾病影响多达 0.3 -1% 的人口。它们是慢性、复发性疾病，可能与明显的损伤和残疾有关。尽管临床护理在过去十年中有所改善，但仍有大量患者对现有治疗没有反应或出现无法忍受的副作用。大多数广泛使用的干预措施最多只能使抽动严重程度降低 30% 至 40%。尽管 TS 的病因尚不清楚，但有关潜在神经回路的新兴知识已被用来指导局灶性脑刺激策略的设计，以研究和治疗抽动障碍。过去十年来，经颅磁刺激 (TMS) 已被用于研究 TS，而至少过去五年，重复 TMS (rTMS) 已被用作严重 TS 的研究性干预措施。最初针对运动和运动前皮层部位（1 Hz 或 15 Hz）的 rTMS 研究在治疗患有严重 TS 的个体方面取得了有限的成功或没有成功。然而，曼托瓦尼等人最近的研究。 (2006) 以辅助运动区 (SMA) 为目标，首次证明 1 Hz rTMS 对 5 名 TS 患者产生了临床显着改善（抽动严重程度降低了 67%）。其中两名患者的抽动症状完全缓解。这些改进维持了三个月。这是一项开放性研究，患者每周接受五天治疗，持续两周，总共 10 次治疗。在治疗过程中或随后的三个月内没有发现重大副作用。这项 II 期临床试验建议复制 Mantovani 等人的研究。 (2006) 使用假刺激控制条件的研究。我们预计筛选 50 名患者并选择 30 名患者参加随机临床试验（15 名患者随机接受假手术，15 名患者接受主动 rTMS）。耶鲁大学和哥伦比亚大学将管理 rTMS 的两个地点。我们将使用盲人、独立的评估者来监测这些干预措施的效果。这项试点/可行性研究将使我们能够对后续 R01 进行准确的功率估计，以在更大的样本中测试 rTMS 对 SMA 的功效和副作用，并检查副作用、次要电生理结果（配对脉冲 TMS 测量运动皮层的兴奋性）、次要临床结果（强迫症状、抑郁症状和注意力缺陷多动障碍） 症状），以及同时服用药物的相对影响。