Behavioral Exercise Training to Reduce Cardiovascular Disease Risk in Men Undergoing Androgen Deprivation Therapy

1项目概要 2本K 01提案的主要目标是使候选人亚历山大卢卡斯博士具备成为 3名能够利用最先进的成像技术评估亚临床 预测癌症患者未来心血管（CV）事件的4种结局， 5个适应（即，锻炼）。接受雄激素阻断治疗（ADT）的前列腺癌（PC）患者 6例发生CV风险因素（身体成分、运动不耐受、代谢 7功能障碍）。运动训练干预是一种有效的非药物方法来管理这些 8治疗的负面影响此外，使用非侵入性方法来确定CV和 9肌肉骨骼贡献者的运动能力可以告知设计更精确的运动处方 10项旨在解决开始ADT的男性中的特定功能缺陷。然而，虽然监督运动训练是 11有效，许多男性缺乏获得这样的计划和建立是否以家庭为基础的行为锻炼 12个方案能有效提高运动能力（峰值VO 2）是很重要的。卢卡斯博士的初步数据 13 PC患者和其他癌症幸存者支持运动训练的可行性和潜力， 14限制治疗副作用。拟议的研究项目将提供重要的关键数据， 15运动训练是否导致有氧健身（峰值VO 2）的改善，以及是否是中央和/或 16外周因素和身体成分是男性峰值VO 2的关键决定因素 17例接受ADT治疗。我们的主要假设是有氧和阻力训练相结合 18干预将通过维持心血管功能，增强氧摄取， 19肌肉，保持瘦体重，并减少脂肪量的积累。我们提出了一个2臂，随机 20项对照试验，以测试12周的家庭和远程提供的运动干预， 21 60名男性接受ADT治疗中高危PC（目标1）。我们将使用高度敏感的，非- 22种有创心脏磁共振（CMR）成像技术与心肺运动试验 23（CPET），以测试干预措施的效果。我们还将确定中央和外周的相对贡献 VO 2峰值的24个组分及其与身体组成的关系（目标2）。调查和定性半 将对完成或退出干预的男性进行25次结构化访谈，以评估 26干预的可接受性，并完善未来干预的内容和交付，以在更大的 27项RCT。这项工作的重点是优化诊断为前列腺癌的男性的心血管健康-这是一个不断增长的 28人口。拟议的K 01将为候选人提供必要的培训，候选人将与 29个专家指导团队，负责研究设计和执行以及职业发展计划。特定 培训的目标是获得设计和进行临床试验的高级技能，从而支持 31.实施旨在改善不同社区健康状况的未来方案。

1 PROJECT SUMMARY 2 A primary goal of this K01 proposal is to equip the candidate, Dr. Alexander Lucas, with the expertise to become 3 an independent investigator who is able to utilize state-of-the-art imaging techniques to evaluate subclinical 4 outcomes that predict future cardiovascular (CV) events in cancer patients, and that respond to behavioral 5 adaptations (i.e., exercise). Prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) 6 experience deleterious changes in CV risk factors (body composition, exercise intolerance, metabolic 7 dysfunction). Exercise training interventions are an effective non-pharmacological approach for managing these 8 negative effects of treatment. Furthermore, the use of non-invasive methods to determine CV and 9 musculoskeletal contributors to exercise capacity can inform the design of more precise exercise prescriptions 10 to address specific functional deficits in men initiating ADT. However, while supervised exercise training is 11 effective, many men lack access to such programs and establishing whether home-based behavioral exercise 12 programs can effectively improve exercise capacity (peak VO2) is important. Dr. Lucas’s preliminary data from 13 PC patients and other populations of cancer survivors support the feasibility and potential of exercise training to 14 limit treatment side effects. The proposed research project will provide critical data important for determining 15 whether exercise training leads to improvements in aerobic fitness (peak VO2), and whether central and/or 16 peripheral factors and components of body composition are key determinants of peak VO2 among men 17 undergoing treatment with ADT. Our primary hypothesis is that a combined aerobic and resistance training 18 intervention will improve peak VO2 by maintaining cardiovascular function, enhancing oxygen extraction at the 19 muscle, maintaining lean body mass, and reducing accumulation of fat mass. We propose a 2-arm, randomized 20 controlled trial to test a 12-week home-based and remotely delivered exercise intervention among 21 60 men undergoing ADT for intermediate to high-risk PC (Aim 1). We will use highly sensitive, non- 22 invasive cardiac magnetic resonance (CMR) imaging techniques with cardiopulmonary exercise testing 23 (CPET) to test effects of the intervention. We will also determine the relative contribution of central and peripheral 24 components of peak VO2 and their association with body composition (Aim 2). Surveys and qualitative semi- 25 structured interviews will be conducted with men who complete or dropout of the intervention to assess 26 intervention acceptability and to refine both content and delivery of a future intervention to be tested in a larger 27 RCT. This work focuses on optimizing cardiovascular health in men diagnosed with prostate cancer – a growing 28 population. The proposed K01 will provide essential training for the candidate, who will work closely with an 29 expert mentoring team with regard to study design and execution and the Career Development Plan. A specific 30 goal of training is to also gain advanced skills in design and conduct of clinical trials thus supporting the 31 implementation of future programs aiming to improve health outcomes in diverse communities.