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