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

描述（由申请人提供）：本提案是为德克萨斯大学西南医学中心精神病学系助理教授Chad Rethorst博士颁发的K 01指导研究科学家发展奖。K 01奖将为Rethorst博士提供必要的额外培训和经验，使其成为研究体力活动对心理健康影响的独立调查员。拟议的职业发展计划包括重点课程，导师从一个多学科小组的既定研究人员和实际研究经验。培训计划侧重于两个培训目标：（1）临床人群RCT设计和实施培训，（2）精神病理学诊断和评估培训，（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博士在设计和进行心境障碍多中心试验方面拥有丰富的经验。史蒂夫·布莱尔博士和托马斯·卡莫迪博士将提供额外的指导。Blair博士在临床人群中使用运动干预进行RCT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的专家。该研究项目是一项运动干预的试点研究，以预防接受干扰素-α（IFN-α）治疗的丙型肝炎患者的抑郁症。IFN-α是丙型肝炎（HPC）的有效治疗方法;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，体力活动可降低未来抑郁症的风险。此外，运动作为抑郁症的独立和/或连续治疗是有效的。参与者将从UT西南肝病临床中心招募，并随机分配到26周的有氧运动组或健康教育对照组。试点研究的目的是：1）检查招募合格HCV患者并将其随机分配至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）分析运动干预预防接受IFN-α治疗的丙型肝炎患者抑郁的初步疗效，（4）对接受IFN-α治疗的HPC患者进行运动干预对IFN-α诱导的抑郁介质的初步影响。成功完成拟议的研究和培训计划将提供必要的知识和经验，以使Rethorst博士朝着他的职业目标前进，成为一名独立的研究者，研究身体活动在治疗和预防精神疾病中的作用。具体而言，从拟议的试点研究中获得的数据将作为在K 01奖的最后一年提交R 01申请的基础。R 01将提出一项有足够把握度的RCT，以检查运动干预预防IFN-α诱导的抑郁症的疗效。

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.