Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression: A double-blind randomized controlled trial

肌酸补充剂和阻力训练可保持肌肉质量并减缓癌症进展：一项双盲随机对照试验

• 批准号: 10712432
• 负责人: Neeraj Agarwal
• 金额: $ 69.26万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712432
• 关键词: Address; Adherence; Adopted; Advanced Malignant Neoplasm; Androgens; Attenuated; Cancer Survivorship; Caring; Castrate sensitive prostate cancer; Clinical; Colorectal Cancer; Complement; Creatine; Disease; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Educational Intervention; Effectiveness; Elasticity; Elderly; Energy Metabolism; Exercise; Exhibits; Fatigue; Fatty acid glycerol esters; Head and Neck Cancer; Health; Home; Incidence; Individual; Institution; Intervention; Intervention Studies; Knowledge; Life Style; Link; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metastatic Prostate Cancer; Modeling; Nonmetastatic; Outcome; Phosphocreatine; Physical Function; Physical Performance; Placebos; Play; Population; Pre-Clinical Model; Proliferating; Protocols documentation; Quality of Care; Quality of life; Randomized; Randomized, Controlled Trials; Reporting; Research; Resistance; Role; Safety; Signal Transduction; Skeletal Muscle; Supplementation; Survival Rate; Survivors; System; Telemedicine; Testing; Thinness; Training Programs; Translating; Vertebral column; Work; analog; androgen deprivation therapy; anti-cancer; cancer biomarkers; cancer survival; cancer therapy; cell free DNA; chemotherapy; double-blind placebo controlled trial; efficacy testing; exercise capacity; exercise training; improved; inhibitor; insulin sensitivity; intervention effect; men; muscle form; patient oriented; preservation; primary outcome; prostate cancer survivors; resistance exercise; survivorship; telehealth; tumor growth; tumor progression; week trial

ABSTRACT The incidence of metastatic prostate cancer has increased 3% per year since 2012, and the survival rate is only 29%. Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). Androgen deprivation therapy (ADT) with an androgen signaling inhibitor is the backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC). But the androgen blockade diminishes muscle mass and contributes to adverse health outcomes critical to mCSPC survivors, such as fatigue, and declines in physical function, independence, insulin sensitivity, and QoL. Resistance training (RT) can preserve muscle mass and improve health outcomes in non-metastatic CSPC survivors receiving ADT. The addition of creatine monohydrate supplementation to an RT program amplifies the effects of RT in cancer-free older adults and other clinical populations. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, creatine monohydrate supplementation with RT (Cr+RT) is a strategy that addresses an important knowledge gap pertaining to survivorship needs of mCSPC survivors. We hypothesize that Cr+RT will preserve muscle mass and improve health outcomes greater than RT alone, and that creatine use will lead to favorable changes in markers of cancer progression in mCSPC survivors receiving ADT. Here we propose a parallel, double-blind randomized controlled trial to test the effects of 52-weeks of Cr+RT compared with placebo (PLA) and RT (PLA+RT) with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT. We will evaluate muscle mass (primary outcome), health outcomes (fatigue, physical function, independence, insulin sensitivity, QoL), and markers or cancer progression (PSA, cfDNA) at baseline, 24-, and 52-weeks. RT will be carried out twice weekly with elastic resistance bands, and we will utilize an established creatine supplementation protocol for creatine and PLA delivery. Our trial builds on work done by our investigative team, and addresses an evidence gap listed in this RFA (CA-22-027: Research to Understand and Address Survivorship Needs of Individuals Living with Advanced Cancer) re: “Interventional research to determine the best ways to improve the quality of care and QoL for individuals living with likely incurable cancer”, identified gaps in the literature, and unmet needs of mCSPC survivors. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. Our approach can be translated on a large-scale as it can be adopted by institutions who use an established telemedicine system, and creatine monohydrate supplementation and elastic resistance bands are inexpensive and widely available. These findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes and QoL, and complement cancer treatment.

摘要 自2012年以来，转移性前列腺癌的发病率每年增加3%，生存率为 只有29%。肌肉质量对转移性前列腺癌的生存和生活质量（QoL）很重要。雄激素 使用雄激素信号传导抑制剂的剥夺疗法（ADT）是治疗患有 转移性去势敏感性前列腺癌（mCSPC）。但是雄激素阻断会减少肌肉质量 并导致对mCSPC幸存者至关重要的不良健康结果，如疲劳， 身体功能、独立性、胰岛素敏感性和生活质量。抗阻训练（RT）可以保护肌肉 扩大并改善接受ADT的非转移性CSPC幸存者的健康结果。添加肌酸 一水化合物补充到RT计划中可以放大RT在无癌症老年人中的作用， 其他临床人群。证据还表明，肌酸补充剂可以补充癌症 治疗因此，补充肌酸一水合物与RT（Cr+RT）是一种策略， 关于mCSPC幸存者生存需求的重要知识差距。我们假设Cr+RT 将保持肌肉质量和改善健康结果大于单独的RT，肌酸的使用将导致 接受ADT的mCSPC存活者中癌症进展标志物的有利变化。在这里，我们提出一个 一项平行、双盲、随机对照试验，旨在检测52周Cr+RT与 安慰剂（PLA）和RT（PLA+RT）与我们的团队建立的，有效的，以家庭为基础的远程医疗RT计划 在接受ADT的200例mCSPC幸存者中。我们将评估肌肉质量（主要结果），健康结果 （疲劳、身体功能、独立性、胰岛素敏感性、QoL）和癌症进展的标志物（PSA， cfDNA）。使用弹性阻力带每周进行两次RT， 我们将利用既定的肌酸补充方案来输送肌酸和PLA。我们的审判 我们的调查团队所做的工作，并解决了本RFA（CA-22-027： 了解和解决晚期癌症患者生存需求的研究）关于： “干预性研究，以确定提高护理质量和生活质量的最佳方法， 可能患有无法治愈的癌症”，确定了文献中的空白，以及mCSPC幸存者未满足的需求。我们 方法解决了一个主要的促进RT在mCSPC幸存者，以家庭为基础的RT计划，同时利用 安全监管模式。我们的方法可以大规模地转化，因为它可以被 使用已建立的远程医疗系统的机构，以及肌酸一水合物补充剂， 弹性阻力带价格低廉且广泛使用。这些发现将改善 通过提供多组分、以患者为中心的生活方式策略， 肌肉质量，改善健康结果和生活质量，并补充癌症治疗。