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，转移性前列腺癌的事件每年增加3％，生存率为 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 具有雄激素信号抑制剂的剥夺治疗（ADT）是男性治疗的骨干 转移性cast割敏感的前列腺癌（MCSPC）。但是雄激素阻滞减少了肌肉质量 并导致对MCSPC表面至关重要的不利健康结果，例如疲劳，并下降 身体功能，独立性，胰岛素敏感性和质量。阻力训练（RT）可以保持肌肉 质量并改善接受ADT的非转移性CSPC表面表面的健康结果。创造的添加 补充RT程序放大器的一水合物在无癌的老年人和 其他临床人群。证据还表明，补充创造可以补充癌症 治疗。那就是肌酸用RT（CR+RT）补充肌酸一水合物 与MCSPC生存的生存需求有关的重要知识差距。我们假设CR+RT 将保留肌肉质量并改善与单独RT相比的健康状况，而创造使用将导致 在接受ADT的MCSPC表面上的癌症进展标记的有利变化。在这里我们提出一个 平行的双盲随机对照试验，以测试52周Cr+RT的影响 安慰剂（PLA）和RT（PLA+RT）与我们团队的建立，有效，基于家庭的远程医疗RT计划 在200个接收ADT的MCSPC表面上。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）以及标记或癌症进展（PSA， CfDNA）在基线，24和52周。 RT每周将通过弹性抵抗带进行两次，然后 我们将利用建立的创建补充协议来创建和PLA交付。我们的审判建立 关于我们的调查团队完成的工作，并解决了此RFA中列出的证据差距（CA-22-027： 了解和满足患有晚期癌症患者的生存需求的研究）回复： 介入的研究以确定改善生活个人护理质量和QOL的最佳方法 可能无法治愈的癌症”，鉴定出文献中的差距，以及MCSPC幸存的需求未满足。 方法是针对基于家庭的RT程序MCSPC冲浪者中RT的主要促进者，同时使用 安全模型的安全模型。我们的方法可以大规模翻译，因为它可以由 使用已建立的远程医疗系统并创建补充一水合物和的机构 弹性电阻带价格便宜且广泛可用。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来保存全面的生存护理 肌肉质量，改善健康结果和质量质量，并补充癌症治疗。