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

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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.