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个项目摘要 2这份K01提案的一个主要目标是让候选人亚历山大·卢卡斯博士具备成为 3能够利用最先进的成像技术评估亚临床的独立研究人员 预测癌症患者未来心血管(CV)事件并对行为做出反应的4种结果 5适应(即锻炼)。前列腺癌患者接受雄激素剥夺治疗(ADT) 6经历心血管危险因素(身体成分、运动不耐受、代谢)的有害变化 7功能障碍)。运动训练干预是一种有效的非药理学方法来管理这些 8治疗的负面影响。此外，使用非侵入性方法来确定CV和 9肌肉骨骼对运动能力的贡献可以为设计更精确的运动处方提供信息 10以解决启动ADT的男性的特定功能缺陷。然而，虽然有监督的运动训练是 有效的是，许多男性无法获得这样的计划，也无法确定是否有家庭行为锻炼 12个方案能有效提高运动能力(VO2峰值)很重要。卢卡斯博士的初步数据来自 13名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关键数据，这些数据对确定 15运动训练是否导致有氧体能(VO2峰值)的改善，以及中枢和/或 16种外周因素和身体成分是男性VO2峰值的关键决定因素 17例正在接受ADT治疗。我们的主要假设是有氧训练和阻力训练相结合 18干预将通过维持心血管功能，增强心脏的氧摄取，改善峰值VO2。 19肌肉，维持瘦身质量，减少脂肪堆积。我们提出了一种随机的双臂 20名对照试验，测试为期12周的基于家庭和远程交付的运动干预 21 60名接受ADT的中高危PC患者(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)，以测试干预效果。我们还将确定中央和外围的相对贡献 24个VO2峰值成分及其与身体成分的关系(目标2)。调查和定性的半 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干预措施的可接受性和精细化的内容和交付的未来干预措施将在一个更大的测试 27个随机对照试验。这项工作的重点是优化被诊断为前列腺癌的男性的心血管健康--一个日益增长的 28人口。拟议的K01将为候选人提供基本培训，候选人将与 29关于研究设计和执行以及职业发展计划的专家指导小组。一种特定的 30培训的目标也是获得设计和进行临床试验的高级技能，从而支持 31执行旨在改善不同社区健康结果的未来方案。