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

摘要 自2012年以来，转移性前列腺癌的发病率每年增长3%，存活率为 只有29%。肌肉质量对转移性前列腺癌的生存和生活质量(QOL)非常重要。雄激素 雄激素信号转导抑制剂的剥夺治疗(ADT)是治疗男性前列腺癌的主要手段。 转移性去势敏感型前列腺癌。但是雄激素的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后果，如疲劳，以及 身体功能、独立性、胰岛素敏感性和生活质量。抵抗力训练(RT)可以保护肌肉 接受ADT的非转移性CSPC幸存者的质量和改善健康结局。肌酸的添加 一水合物补充RT计划放大了RT对无癌老年人和 其他临床人群。也有证据表明补充肌酸可以补充癌症。 治疗。因此，一水肌酸补充RT(铬+RT)是一种解决 与mcpc幸存者的生存需求有关的重要知识缺口。我们假设铬+RT 将比单独使用RT更能保护肌肉质量和改善健康结果，而且肌酸的使用将导致 在接受ADT的mCSPC幸存者中，肿瘤进展标志物的有利变化。在这里，我们提出一种 平行、双盲随机对照试验，比较52周铬+放疗与常规放疗的疗效 安慰剂(解放军)和RT(解放军+RT)与我们团队建立的、有效的、基于家庭的远程医疗RT计划 200例接受ADT治疗的MCSPC幸存者。我们将评估肌肉质量(主要结果)、健康结果 (疲劳、身体功能、独立性、胰岛素敏感性、QOL)和标记物或癌症进展(PSA、 CfDNA)在基线、24周和52周。使用弹性阻力带每周进行两次RT，以及 我们将利用已建立的肌酸补充方案来提供肌酸和解放军。我们的试验建立了 关于我们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)回复： “介入研究，以确定改善个人生活质量和生活质量的最佳方法 可能是无法治愈的癌症“，确定了文献中的空白，以及mCSPC幸存者未得到满足的需求。我们的 该方法解决了mCSPC幸存者中RT的主要促进者，这是一个基于家庭的RT计划，同时利用 安全监督模型。我们的方法可以大规模翻译，因为它可以被 使用已建立的远程医疗系统和一水肌酸补充以及 弹性阻力带价格便宜，而且随处可见。这些发现将改善交付 通过提供多组件、以患者为中心的生活方式策略来提供全面的生存护理 肌肉质量，改善健康结果和生活质量，并补充癌症治疗。

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.