Behavior Therapy for Adults with Tourette Syndrome

描述（由申请人提供）：Tourette综合征（TS）是一种神经系统疾病，其特征为持续性运动和发声抽搐。抽搐可以是面部、肩部和四肢的短暂、快速和快速的运动，也可以是更复杂和有目的的外观。声音抽搐可以是简单的声音，如嗅或咕噜声或更复杂的声音，包括重复的单词和短语。抽搐随着时间的推移而增加和减少，在10至12岁之间达到高峰。然而，有些人有一个更持久的抽搐过程到成年。当出现在成年人身上时，TS的抽搐可能与相当大的痛苦、社会和职业障碍以及歧视有关。大量证据表明，涉及丘脑、基底神经节和额叶皮质的皮质-皮质下通路功能障碍。虽然以神经学为基础，但行为和环境因素也可能在抽搐维持中发挥作用。目前，抽搐抑制的标准治疗是药物治疗，特别是中枢作用的多巴胺阻断药物。然而，这些药物与一系列不良反应有关，可能导致依从性差或过早终止治疗。此外，目前可用的药物很少消除所有抽搐。因此，在管理他们的慢性病时，成年人往往面临对药物的部分反应，或者由于不可接受的副作用而选择避免所有药物。本申请中列出的研究人员的初步研究表明，一种名为习惯逆转训练（HRT）的行为治疗是一种有希望的抽搐干预措施。HRT是一种多成分治疗方法，包括意识训练、自我监测、应急管理、不便回顾、放松训练和竞争反应。HRT被设计为单药治疗和/或作为药物治疗的增强。虽然最初的研究评价HRT在TS的疗效一直令人鼓舞，迄今为止的调查一直是个案研究或小型随机试验，HRT从未被系统地研究作为一种增强药物治疗。 作为对项目公告PA 01-123的回应，本申请描述了一项多中心调查，以评估结构化HRT项目对TS成人抽动减少的疗效。为了进行这项研究，图雷特综合征协会（TSA）召集了行为科学联盟（BSC）。BSC是一个多学科研究小组，代表了美国一些领先的TS研究项目，包括耶鲁大学、马萨诸塞州总医院（MGH）/哈佛医学院、加州大学洛杉矶分校（UCLA）和约翰霍普金斯大学。另外两个中心，威尔福德霍尔医学中心/德克萨斯大学圣安东尼奥健康科学中心（WHMC/UTHSCSA）和威斯康星大学密尔沃基分校（UWM），有在HRT的具体专业知识的调查。BSC的使命是为TS患者开发、测试和传播行为干预。在这项拟议的研究中，120名合格的参与者将被随机分配接受HRT或增强支持性心理治疗。两种治疗均包括12周内的10次治疗，随后是2次加强治疗以及3个月和6个月的随访评估。关注的主要结局将是由对治疗分配不知情的独立评估者评估的抽搐严重程度的变化。还将评价HRT作为抽搐单药治疗和作为持续稳定的抽搐抑制药物的强化治疗的效果。三个研究招募中心为MGH/哈佛、WHMC/UTHSCSA和耶鲁大学。来自UCLA和UWM的研究者将通过单独的分包合同提供特定的质量保证和评估服务，并将组建数据安全和监测委员会（DSMB）以进行数据和安全监测。耶鲁大学的信息学小组将提供数据管理服务。

DESCRIPTION (provided by applicant): Tourette Syndrome (TS) is a neurological disorder characterized by persistent motor and vocal tics. Tics can be brief, rapid and darting movements of the face, shoulders, and extremities or more complex and purposeful in appearance. Vocal tics can be simple sounds such as sniffing or grunting or more complex sounds including repeated words and phrases. Tics wax and wane over time with peak severity between ages 10 and 12 years. However, some individuals have a more enduring course of tics into adulthood. When present in adults, the tics of TS can be associated with considerable distress, social and occupational impairment, and discrimination. A substantial body of evidence implicates dysfunction of cortical-subcortical pathways involving the thalamus, basal ganglia and the frontal cortex. Although neurologically-based, behavioral and environmental factors may also play a role in tic maintenance. Currently, the standard treatment for tic suppression is medication, particularly centrally acting dopamine-blocking drugs. However, these medications are associated with a range of adverse effects that can result in poor compliance or in premature termination of treatment. Moreover, currently available medications rarely eliminate all tics. Thus, when managing their chronic condition, adults are often faced with a partial response to medication, or they opt to avoid all medications due to unacceptable side effects. Preliminary research by the investigators listed on this application suggests that a behavioral treatment called habit reversal training (HRT) is a promising intervention for tics. HRT is a multi-component treatment approach that includes awareness training, selfmonitoring, contingency management, inconvenience review, relaxation training and competing responses. HRT is designed as a monotherapy and/or as an augmentation to pharmacotherapy. Although the initial studies evaluating the efficacy of HRT in TS have been encouraging, to date the investigations have been case studies or small randomized trials, and HRT has never been systematically investigated as an augmentation to pharmacotherapy. In response to Program Announcement PA 01-123, this application describes a multisite investigation to evaluate the efficacy of a structured HRT program for tic reduction in adults with TS. To conduct this study, the Tourette Syndrome Association (TSA) assembled the Behavioral Sciences Consortium (BSC). The BSC is a multidisciplinary group of investigators representing some of the leading TS research programs in the country including Yale, Massachusetts General Hospital (MGH)/Harvard Medical School, University of California at Los Angeles (UCLA), and Johns Hopkins. Two additional centers, Wilford Hall Medical Center/University of Texas Health Sciences Center at San Antonio (WHMC/UTHSCSA), and the University of Wisconsin-Milwaukee (UWM), have investigators with specific expertise in HRT. The mission of the BSC is to develop, test, and disseminate behavioral interventions for patients with TS. In this proposed study, 120 eligible participants will be randomly assigned to receive either HRT or Enhanced- Supportive Psychotherapy. Both treatments will consist of 10 sessions over 12 weeks followed by 2 booster sessions and 3- and 6-months follow up assessments. The primary outcome of interest will be change in tic severity assessed by an independent evaluator blind to treatment assignment. The effect of HRT as a monotherapy for tics and as augmentation to ongoing, stable tic-suppressing medication will also be evaluated. The three study recruitment sites are MGH/Harvard, WHMC/UTHSCSA, and Yale University. Investigators from UCLA and the UWM will provide specific quality assurance and assessment services via separate subcontracts, and a Data Safety and Monitoring Board (DSMB) will be assembled for data and safety monitoring purposes. The Informatics group at Yale University will provide data management services.