The Feasibility and Acceptability of Resistance Training and Creatine Supplementation to Promote Physical Function in Sarcopenic Colorectal Cancer Survivors

结直肠癌是世界上第三大最常见的癌症。肌肉减少症，定义为 骨骼肌质量和功能，在结直肠癌中非常普遍，据报道发病率高达60%。 癌症中的肌肉减少症病因是多因素的，随着年龄的增长和不活动，治疗毒性， 营养不良、肿瘤负荷和高度炎症。因此，单峰不太可能 干预措施将足以克服该人群中肌肉减少症的负担。肌酸一水合物 是体内天然存在的化合物，在运动期间的能量供应中起着关键作用。 肌酸是迄今为止研究最广泛的营养补充剂，有超过1,000项研究证实其 在男性、女性和老年人以及其他临床人群中的安全性和有效性。有 强有力的和一致的证据表明，肌酸补充剂可以增强积极的适应， 老年人和临床人群的阻力训练。因此，有强大的潜力， 应用肌酸和抗阻训练来抵消癌症后肌肉质量和功能的下降 治疗建议研究的目的是检查肌酸的可行性和可接受性 补充与阻力运动相结合，与单独进行阻力运动相比， 患有结肠直肠癌的病人我们提出了一个随机对照试验，检查 10周多模式抗阻运动和肌酸补充（EXSUPP）（n = 20）相对于 单独抗阻运动（EXPLA）（n = 20）治疗患有肌肉减少症的结直肠癌患者。 该项目的具体目标是：1）确定干预措施的可行性和可接受性， 大肠癌患者？癌症治疗后被诊断为肌肉减少症，2）比较 运动和肌酸补充干预（EXSUPP）到单独运动（EXPLA）对身体的影响 组成，肌肉力量，身体功能和生活质量和3）探索肌肉分子水平 适应，即，线粒体健康和蛋白质周转，以响应干预措施。该项目将 第一个将联合收割机运动与肌酸结合起来的人，专门针对以前患有肌肉减少症的人 治疗结直肠癌该项目直接符合NCI的优先研究计划 Cancer MoonshotSM旨在“最大限度地减少癌症治疗的衰弱副作用”。我们的试验是创新的， 解决了结肠直肠癌患者最重要的健康问题之一， 成为第一个1）检查多模式运动和营养干预的可行性和可接受性 相对于单独锻炼治疗结肠直肠癌的肌肉减少症患者，2）探索 运动和营养干预反应的分子机制。

Colorectal cancer is the third most commonly diagnosed cancer in the world. Sarcopenia, defined as a loss of skeletal muscle mass and function, is highly prevalent in colorectal cancer, with rates of up to 60% reported. Sarcopenia etiology in cancer is multifactorial, with aging and inactivity compounded by treatment toxicities, malnutrition, tumor burden, and high-grade inflammation. Consequently, it’s unlikely that unimodal interventions will be sufficient to overcome the burden of sarcopenia in this population. Creatine monohydrate is a naturally occurring compound in the body that plays a critical role in energy provision during exercise.4 Creatine is the most widely studied nutritional supplement to date, with well over 1,000 studies establishing its safety and effectiveness in men, women and older adults, in addition to other clinical populations. There is strong and consistent evidence that creatine supplementation can enhance the positive adaptations to resistance training in older adults and clinical populations. Therefore, there is strong potential for the application of creatine and resistance training to offset the decline in muscle mass and function after cancer treatment. The purpose of the proposed study is to examine the feasibility and acceptability of creatine supplementation combined with resistance exercise, compared to resistance exercise alone in individuals treated for colorectal cancer who are sarcopenic. We propose a randomized controlled pilot trial, examining the effects of 10-week multimodal resistance exercise and creatine supplementation (EXSUPP) (n=20) relative to resistance exercise alone (EXPLA) (n=20) in individuals treated for colorectal cancer who have sarcopenia. The specific aims of this project are to 1) determine the feasibility and acceptability of the intervention in colorectal cancer patients? diagnosed with sarcopenia after cancer treatment, 2) compare the effects of an exercise and creatine supplementation intervention (EXSUPP) to exercise alone (EXPLA) on body composition, muscle strength, physical function, and quality of life and 3) explore muscle molecular-level adaptations, i.e., mitochondrial health and protein turnover, in response to the interventions. This project will be one of the first to combine exercise with creatine, specifically targeting sarcopenia in individuals previously treated for colorectal cancer. This project is directly in line with the priority research initiative from the NCI Cancer MoonshotSM to “minimize Cancer Treatment’s Debilitating Side Effects.” Our trial is innovative in addressing one of the most important health problems for individuals treated for colorectal cancer in that it will be the first to 1) examine the feasibility and acceptability of a multimodal exercise and nutritional intervention relative to exercise alone in individuals treated for colorectal cancer who are sarcopenic and 2) explore the molecular mechanisms underpinning the response to exercise and nutritional interventions.