EFFECTIVENESS OF MULTI-DRUG TREATMENTS IN TOURETTE'S

该K23申请的目的是为候选人成为一名独立研究者做好准备，能够设计、获得资金，并在同时发生神经和精神疾病的儿童中进行有效的临床试验。候选人提出了一个独特的和良好整合的教育经验组合：1)指导在精神病学，神经病学和结果研究方面建立临床试验的研究人员；2)在统计和研究设计方面有严格的硕士培训计划，在18个月内每月有30小时的课堂时间。候选人建议在患有图雷特综合症的儿童和青少年的多药物治疗的临床有效性试验中实施经验教训，图雷特综合症是一种同时发生的神经和精神症状的范式障碍。图雷特氏综合症是一种神经精神疾病，其特征是超过一年的运动和声音抽搐，并对功能或社交造成干扰。儿童和青少年经常同时患有多种神经精神诊断，并且使用从未一起测试过的药物组合进行治疗。目前的临床研究通常涉及单一疗法的疗效研究，可能具有有限的临床相关性。本次K奖的研究计划包括一项随机对照的多巴胺激动剂培高利特的临床有效性研究，允许同时治疗合并症。主要假设是培高利特治疗将与显著的抽动抑制相关，独立于同时治疗强迫症或多动症。该研究将有能力确定是否存在治疗的共病强迫症或多动症在药物治疗后抽搐症状变化的显著差异。赠款的另一个重点将是制定这种疾病的保健利用和费用措施，并确定它们与缺乏有效症状管理的关系。

The purpose of this K23 proposal is to prepare the candidate to become an independent investigator, able to design, acquire funding for, and perform valid clinical trials in children with co-occurring neurologic and psychiatric disorders. The candidate proposes a unique and well- integrated combination of educational experiences: 1) mentorship with established clinical trials researchers in psychiatry, neurology, and outcomes research; and 2) a rigorous master's training program in statistics and research design, with 30 hours of classroom time per month over 18 months. The candidate proposes to implement the lessons learned in a clinical effectiveness trial of multi-drug treatments in children and adolescents with Tourette's Syndrome, a paradigm disorder of co-occurring neurologic and psychiatric symptoms. Tourette's Syndrome is a neuropsychiatric disorder characterized by greater than one year of motor and vocal tics that are functionally or socially disturbing. Children and adolescents frequently have multiple co-occurring neuropsychiatric diagnoses and are treated with combinations of medications that have never been tested together. Current clinical research typically involves efficacy studies of monotherapy that may have limited clinical relevance. The research proposal of this K award includes a randomized controlled clinical effectiveness study of a dopamine agonist, pergolide, allowing for concurrent treatment of comorbid disorders. The primary hypothesis is that treatment with pergolide will be associated with significant tic suppression, independent of concurrent treatment for OCD or ADHD. The study will have the power to determine whether the presence of treated co-morbid OCD or ADHD accounts for significant variance in the change in tic symptoms on medication. An additional focus of the grant will be developing measures of health care utilization and costs in this disorder and determining their relationship to the presence of absence of effective symptom management.