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.

抽象的 自2012年以来，转移性前列腺癌的发病率每年增加3%，生存率 只有29%。肌肉质量对于转移性前列腺癌的生存和生活质量 (QoL) 很重要。雄激素 使用雄激素信号抑制剂的剥夺疗法 (ADT) 是男性治疗的支柱 转移性去势敏感前列腺癌（mCSPC）。但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，例如疲劳和能力下降 身体机能、独立性、胰岛素敏感性和生活质量。阻力训练（RT）可以保护肌肉 质量并改善接受 ADT 的非转移性 CSPC 幸存者的健康结果。添加肌酸 在 RT 计划中补充一水合物可增强 RT 对无癌老年人的影响 其他临床人群。有证据还表明补充肌酸可以补充癌症 治疗。因此，补充一水肌酸和 RT (Cr+RT) 是解决以下问题的一种策略： 有关 mCSPC 幸存者生存需求的重要知识差距。我们假设 Cr+RT 与单独放疗相比，可以更好地保留肌肉质量并改善健康结果，并且肌酸的使用将导致 接受 ADT 的 mCSPC 幸存者的癌症进展标志物发生有利变化。在这里我们提出一个 平行、双盲随机对照试验，测试 52 周 Cr+RT 与 安慰剂 (PLA) 和 RT (PLA+RT) 与我们团队已建立的、有效的、以家庭为基础的远程医疗 RT 计划 200 名接受 ADT 的 mCSPC 幸存者。我们将评估肌肉质量（主要结果）、健康结果 （疲劳、身体机能、独立性、胰岛素敏感性、生活质量）以及癌症进展标志物（PSA、 cfDNA）在基线、24 周和 52 周时。 RT 将每周进行两次，使用弹性阻力带，并且 我们将利用既定的肌酸补充方案来输送肌酸和 PLA。我们的试用版 我们的调查团队所做的工作，并解决了本 RFA (CA-22-027: 研究了解和解决晚期癌症患者的生存需求）： “干预研究旨在确定提高个人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。 该方法解决了 mCSPC 幸存者 RT 的主要促进因素，这是一项基于家庭的 RT 计划，同时利用 安全监督模型。我们的方法可以大规模转化，因为它可以被采用 使用已建立的远程医疗系统和一水肌酸补充剂的机构 弹性阻力带价格低廉且广泛使用。这些发现将改善交付 通过提供多组成部分、以患者为中心的生活方式策略来维持全面的生存护理 肌肉质量，改善健康结果和生活质量，并补充癌症治疗。