Pramipexole in Treatment-Resistant Depression

描述（由申请人提供）：这是一个指导患者为导向的职业发展（K23）奖申请的重新提交，以提高申请人在治疗难治性抑郁症的创新疗法研究的专业知识。本申请的研究部分包括一项随机、双盲、安慰剂对照试验，研究多巴胺受体激动剂普拉克索治疗难治性抑郁症。接受随机化治疗后病情改善的受试者也将进入一项继续阶段初步研究。该应用程序利用创新的疗法和简单，严格的设计来解决对公共卫生产生重大影响的未充分研究的疾病。初步研究表明，多巴胺受体激动剂（如普拉克索）对这些患者可能有效，但最佳剂量尚未确定。本研究的主要目的是确定与安慰剂相比，灵活给药的普拉克索的疗效。次要分析将包括缓解的临床预测因素。在奖励期的最后两年，候选人将根据这些数据并利用其正式培训进行更大规模的研究。拟议的研究将在马萨诸塞州总医院的抑郁症临床和研究项目中进行，由Andrew Nierenberg，M.D.指导。和Maurizio Fava，M.D.的共同指导，A.约翰·拉什医学博士和迈克尔·塞斯医学博士与当地和国家专家小组协商。该应用程序还包括一个丰富的教学组成部分，将哈佛公共卫生学院的正式课程与研究设计，治疗抗性评估和管理，生物统计学和生物伦理学的教程相结合。由于共同导师是两个大型NIMH资助的情绪障碍有效性研究的共同首席研究员或首席研究员，候选人还将参与两项研究的统计审查和持续分析，应用他的课程和教程中开发的技能。拟议的调查和培训计划将提供关键技能，经验和数据，以帮助候选人撰写R01并成为独立调查员。

DESCRIPTION (provided by applicant): This is a resubmission of a Mentored Patient-Oriented Career Development (K23) Award application to enhance the applicant's expertise in the study of innovative therapies for treatment-resistant major depression. The research component of this application includes a randomized, double-blind, placebo controlled trial of adjunctive pramipexole, a dopamine receptor agonist, for treatment-resistant depression. Subjects who improve with randomized treatment will also enter a continuation-phase pilot study. The application utilizes an innovative therapy and a simple, rigorous design to address an understudied disorder with major impact on public health. Preliminary studies suggest augmentation with dopamine receptor agonists such as pramipexole may be efficacious in these patients, though the optimum dose has not been established. The primary aim of this study will be to determine the efficacy of flexibly-dosed pramipexole compared to placebo. Secondary analyses will include clinical predictors of response. During the final two years of the award period, the candidate will develop a larger study building on this data and drawing on his formal training. The proposed study will be conducted at Massachusetts General Hospital in the Depression Clinical and Research Program, under the mentorship of Andrew Nierenberg, M.D. and co-mentorship of Maurizio Fava, M.D., A. John Rush, M.D., and Michael Thase, M.D., with consultation from a panel of local and national experts. The application also includes a rich didactic component combining formal coursework at the Harvard School of Public Health with tutorials in study design, assessment and management of treatment resistance, biostatistics, and bioethics. As the co-mentors are co-principal investigator or principal investigator in two large NIMH-funded effectiveness studies in mood disorders, the candidate will also participate in statistical review and ongoing analysis of both studies, applying skills developed in his coursework and tutorials. The proposed investigation and training program will provide critical skills, experience and data to aid the candidate in writing an R01 and becoming an independent investigator.