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

行为运动训练可降低接受雄激素剥夺治疗的男性心血管疾病风险

• 批准号: 10740615
• 负责人: Alexander Russell Lucas
• 金额: $ 12.35万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-25 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740615
• 关键词: Acceleration; Activities of Daily Living; Address; Adoption; Aerobic Exercise; Age; Behavior Therapy; Behavioral; Body Composition; Buffers; Cancer Center; Cancer Patient; Cancer Survivor; Cardiac; Cardiac Output; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Clinic; Clinical Trials; Communities; Conduct Clinical Trials; Data; Development Plans; Diagnosis; Dropout; Education; Educational Intervention; Effectiveness; Environment; Event; Exercise; Exercise Test; Fatigue; Fatty acid glycerol esters; Functional disorder; Future; Geography; Goals; Guidelines; Health; Health education; Heart failure; Home; Imaging Techniques; Impairment; Individual; Intervention; Interview; Intramuscular; Learning Module; Left; Magnetic Resonance; Maintenance; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical center; Mentored Research Scientist Development Award; Mentors; Metabolic; Metabolic syndrome; Methodology; Methods; Morbidity - disease rate; Muscle; Musculoskeletal; Musculoskeletal System; Myocardial dysfunction; Obesity; Outcome; Oxygen; Participant; Patients; Peripheral; Physical Function; Physical activity; Population; Prostate Cancer therapy; Qualifying; Race; Randomized; Research; Research Design; Research Personnel; Research Project Grants; Sampling; Skeletal Muscle; Structure; Surveys; Symptoms; Testing; Training; Training Programs; Treatment Side Effects; United States Department of Veterans Affairs; Venous; Ventricular; Virginia; Walking; Work; aged; androgen deprivation therapy; arm; cardiac magnetic resonance imaging; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career; career development; comparison control; coronary fibrosis; design; disorder risk; effective intervention; evidence base; exercise capacity; exercise intervention; exercise intolerance; exercise prescription; exercise program; exercise training; experience; future implementation; health care availability; health related quality of life; heart function; high risk; improved; insight; intervention effect; intervention refinement; intraperitoneal; lean body mass; male; men; mortality; muscle form; novel; older men; outcome prediction; preservation; programs; prostate cancer risk; recruit; remote delivery; resistance exercise; skills; strength training; therapy design; treatment effect; vigorous intensity

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.

1 项目概要 2 K01 提案的主要目标是为候选人 Alexander Lucas 博士提供专业知识，使其成为 3 能够利用最先进的成像技术来评估亚临床的独立研究者 预测癌症患者未来心血管 (CV) 事件并对行为做出反应的 4 个结果 5 适应（即运动）接受雄激素剥夺治疗（ADT）的前列腺癌（PC）患者。 6 经历了心血管风险因素的有害变化（身体成分、运动不耐受、代谢 7 功能障碍）运动训练干预是管理这些功能的有效非药物方法。 8.此外，使用非侵入性方法来确定CV和治疗的负面影响。 运动能力的 9 个肌肉骨骼因素可以为设计更精确的运动处方提供参考 10 解决开始 ADT 的男性的特定功能缺陷 然而，虽然监督运动训练是有效的。 11 有效的，许多男性缺乏获得此类计划的机会，并确定是否进行家庭行为锻炼 12个项目可以有效提高运动能力（峰值摄氧量），卢卡斯博士的初步数据很重要。 13 名 PC 患者和其他癌症幸存者群体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对于确定重要的关键数据。 15 运动训练是否会改善有氧健身（峰值摄氧量），以及中枢和/或 16 个外围因素和身体成分组成是男性峰值摄氧量的关键决定因素 17 正在接受 ADT 治疗 我们的主要假设是有氧训练和阻力训练相结合。 18 干预措施将通过维持心血管功能、增强氧摄取量来提高峰值摄氧量 19 肌肉，保持瘦体重，并减少脂肪量的积累我们提出了 2 臂，随机。 20 项对照试验，测试为期 12 周的家庭远程运动干预 21 60 名男性接受 ADT 治疗中高风险 PC（目标 1）。 22 种侵入式心脏磁共振 (CMR) 成像技术与心肺运动测试 23 (CPET) 来测试干预效果，我们还将确定中枢和外周的相对贡献。 峰值摄氧量的 24 个组成部分及其与身体成分的关联（目标 2）。 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 干预措施的可接受性，并完善未来干预措施的内容和实施方式，以在更大范围内进行测试 27 随机对照试验。这项工作的重点是优化被诊断患有前列腺癌的男性的心血管健康——这是一种日益严重的癌症。 28 人口。拟议的 K01 将为候选人提供必要的培训，他们将与一个人密切合作。 29 名专家指导团队负责研究设计和执行以及具体的职业发展计划。 30 培训目标还在于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计划。