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: 7361890
• 负责人: JAMES F LECKMAN
• 金额: $ 23.85万
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361890
• 关键词: Adult; Adverse effects; Affect; Area; Attention deficit hyperactivity disorder; Bilateral; Brain; Caring; Chronic; Clinical; Condition; Data; Disease; Disease remission; Double-Blind Method; Effectiveness of Interventions; Etiology; Feasibility Studies; Gilles de la Tourette syndrome; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Measures; Mental Depression; Mink; Monitor; Motor; Motor Cortex; Numbers; Obsessive-Compulsive Disorder; Outcome; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Physiologic pulse; Population; Pulse taking; Randomized; Randomized Clinical Trials; Relapse; Relative (related person); Reporting; Safety; Sampling; Screening procedure; Severities; Site; Symptoms; Testing; Therapeutic; Tic disorder; Transcranial magnetic stimulation; Week; blind; clinically significant; day; depressive symptoms; design; disability; experience; improved; 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(申请人提供)：抽动秽语综合征(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，可能与明显的损害和残疾有关。尽管临床护理在过去十年中有所改善，但相当数量的患者对可用的治疗没有反应，或者经历了无法忍受的副作用。大多数广泛使用的干预措施最多只能将抽搐的严重程度降低30%到40%。虽然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于指导设计局灶性脑刺激策略来研究和治疗抽动障碍。在过去的十年中，经颅磁刺激(TMS)被用于TS的研究，而重复TMS(RTMS)至少在过去的五年中被用于重度TS的研究干预。最初的rTMS研究针对1赫兹或15赫兹的运动和运动前皮质部位，在治疗严重TS患者方面有限或没有成功。然而，Mantovani等人最近的研究。(2006)以补充运动区(SMA)为目标的研究首次证明，1赫兹rTMS在5名TS患者中产生了临床显着改善(抽动严重程度降低67%)。其中两名患者的抽搐症状完全缓解。这些改善持续了三个月。这是一项开放式研究，患者每周接受五天治疗，为期两周，总共接受10次治疗。在治疗过程中或随后的三个月中，没有发现重大副作用。这项第二阶段临床试验计划复制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名随机进入假手术组，15名接受活动性rTMS治疗)。两个网站将管理rTMS，耶鲁大学和哥伦比亚大学。我们将使用一名盲目的独立评估员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的R01进行准确的功率估计，以在更大的样本中测试rTMS对SMA的疗效和副作用，并检查副作用、次级电生理结果(双脉冲TMS，以测量运动皮质的兴奋性)、次级临床结果(强迫症、抑郁症状和注意力缺陷多动障碍症状)，以及同时用药的相对影响。