An Exercise Intervention to Prevent Interferon-Induced Depression in Hepatitis C

描述（由申请人提供）：本提案为德克萨斯大学西南医学中心精神病学助理教授Chad Rethorst博士申请K01指导研究科学家发展奖。K01奖将为Rethorst博士提供额外的培训和必要的经验，使其成为一名研究体育活动对心理健康影响的独立研究者。拟议的职业发展计划包括重点课程、由知名研究人员组成的多学科小组的指导和实际研究经验。培训计划侧重于两个培训目标：(1)临床人群随机对照试验的设计和实施培训；(2)精神病理诊断和评估培训；(3)生物统计学方法高级培训。Madhukar Trivedi博士将担任主要导师并监督培训计划。Trivedi博士在情绪障碍多地点试验的设计和实施方面拥有丰富的经验。Steve Blair博士和Thomas Carmody博士将提供额外的指导。布莱尔博士在临床人群中使用运动干预进行随机对照试验方面拥有丰富的经验。卡莫迪博士是心理健康领域研究设计和项目纵向分析方面的专家。该研究项目是一项对接受干扰素-α (IFN-α)治疗的丙型肝炎患者进行运动干预以预防抑郁的试点研究。IFN-α是治疗丙型肝炎（HPC）的有效药物；然而，IFN-α治疗导致抑郁症状显著增加。在IFN-α治疗期间，运动干预预防抑郁症的潜力得到了纵向数据的支持，这些数据表明，体育活动可以降低未来抑郁症的风险。此外，运动作为单独和/或辅助治疗抑郁症是有效的。参与者将从西南大学肝脏疾病临床中心招募，随机分为26周：有氧运动组或健康教育对照组。试点研究的目的是：1)检查招募和随机化符合条件的HCV患者进入RCT的可行性；2)检查在整个试验期间保持参与者参与的可行性；3)分析运动干预对接受IFN-α治疗的丙型肝炎患者预防抑郁的初步疗效。4)分析运动干预对接受IFN-α治疗的HPC患者IFN-α诱导抑郁的介质的初步影响。该研究和培训计划的成功完成将为Rethorst博士的职业目标提供必要的知识和经验，他的职业目标是成为一名独立的研究者，研究体育活动在治疗和预防精神疾病中的作用。具体地说，从建议的试验研究中获得的数据将作为在K01奖的最后一年提交R01申请的基础。R01将提出一项足够有力的随机对照试验，以检验运动干预在预防IFN-α-诱导的抑郁症中的功效。

DESCRIPTION (provided by applicant): This proposal is for a K01 Mentored Research Scientist Development Award for Dr. Chad Rethorst, Assistant Professor in the Department of Psychiatry at University of Texas Southwestern Medical Center. The K01 award will provide the Dr. Rethorst with the additional training and experience necessary to become an independent investigator studying the effects of physical activity on mental health. The proposed career development plan includes focused coursework, mentorship from a multi-disciplinary group of established researchers and practical research experience. The training plan focuses on two training objectives: (1) training in the design and conduct of RCTs in clinical population, (2) training in psychopathology diagnosis and assessment and (3) advanced training in biostatistical methods. Dr. Madhukar Trivedi will serve as the primary mentor and will oversee the training plan. Dr. Trivedi has extensive experience in the design and conduct of multisite trials in mood disorders. Dr. Steve Blair and Dr. Thomas Carmody will provide additional mentorship. Dr. Blair has extensive experience in conducting RCTs using exercise interventions in clinical populations. Dr. Carmody is an expert in study design and longitudinal analysis of projects in the area of mental health. The research project is a pilot study of an exercise intervention to prevent depression in Hepatitis C patients receiving Interferon-alpha (IFN-α) treatment. IFN-α is an efficacious treatment for Hepatitis C (HPC); however, IFN-α treatment results in a significant increase in depressive symptoms. The potential of an exercise intervention to prevent depression during IFN-α treatment is supported by longitudinal data demonstrating that physical activity reduces future risk of depression. Furthermore, exercise is efficacious as a stand-alone and/or adjunctive treatment for depression. Participants will be recruited from the Clinical Center for Liver Diseases at UT-Southwestern and randomized to 26 weeks of either: aerobic exercise or a health education control group. The aims of the pilot study are: 1) to examine the feasibility of recruitment and randomization of eligible HCV patients into an RCT, 2) to examine the feasibility of maintaining participant engagement throughout the duration of the trial, 3) to conduct an analysis of the preliminary efficacy of an exercise intervention in preventing depression in Hepatitis C patients receiving IFN-α treatment, and 4) to conduct an analysis of the preliminary effects of an exercise intervention on mediators of IFN-α induced depression in HPC patients receiving IFN-α treatment. The successful completion of the proposed research and training plan will provide the knowledge and experience necessary to progress Dr. Rethorst toward his career goal of becoming an independent investigator examining the role of physical activity in the treatment and prevention of mental illness. Specifically, the data obtained from the proposed pilot study will serve as the basis for an R01 application to be submitted during the final year of the K01 award. The R01 will propose an RCT sufficiently powered to examine the efficacy of an exercise intervention in the prevention of IFN-α-induced depression.