D3-creatine dilution to determine skeletal muscle mass in colon cancer patients

D3-肌酸稀释液测定结肠癌患者的骨骼肌质量

• 批准号: 10579981
• 负责人: Elizabeth Marjorie Cespedes Feliciano
• 金额: $ 38万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579981
• 关键词: Abdomen; Acceleration; Affect; Aging; Area; Biological Markers; Blood Pressure; Cancer Patient; Carcinoembryonic Antigen; Cessation of life; Clinical; Colon Carcinoma; Colorectal Cancer; Connective Tissue; Creatine; Creatinine; Data; Dose; Dose Limiting; Dual-Energy X-Ray Absorptiometry; Enrollment; Fascia; Fasting; Funding; Future; Glucose; Hand Strength; Inflammation; Inflammatory; Intervention; Lead; Lipids; Low Prevalence; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Methods; Monitor; Morbidity - disease rate; Muscle; Muscle Proteins; Muscular Atrophy; Nonmetastatic; Oncology; Oral; Organ; Outcome; Patient Participation; Patients; Performance Status; Physical Function; Physical Performance; Physical activity; Proxy; Radiation; Randomized; Randomized, Controlled Trials; Recurrent disease; Regional Anatomy; Research; Risk; Risk Factors; Role; Sampling; Sarcomeres; Scanning; Site; Skeletal Muscle; Skin; Spottings; Surgical complication; Testing; Thinness; Time; Tissues; Toxic effect; Toxicity due to chemotherapy; Treatment Side Effects; United States; Urine; Validation; Waiting Lists; Water; X-Ray Computed Tomography; cancer diagnosis; cancer risk; cancer survival; cardiometabolic risk; chemotherapy; cohort; colon cancer patients; colorectal cancer risk; comparison intervention; cost effective; design; disability; exercise intervention; fall injury; functional disability; functional status; intervention effect; lean body mass; mortality; muscle form; older men; participant enrollment; reduced muscle mass; resistance exercise; response; standard of care; surgical risk; therapy outcome; tool; treatment risk

ABSTRACT Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the United States. Using clinically- acquired computed tomography (CT) scans to measure muscle cross-sectional area (CSA), the prevalence of low muscle in nonmetastatic CRC patients is estimated to be 42%. Low CT CSA has been associated with a more than 2-fold increased risk of chemotoxicity, a 26% increased risk of surgical complication and a 46% increased risk of CRC-specific death. However, the use of CT to estimate muscle mass is constrained because CT is not the standard of care in all cancers, is often limited to one anatomic region and cannot distinguish between contractile muscle protein and other tissue in muscle fascia. Alternatives include dual energy x-ray absorptiometry (DXA), which measures all lean body mass (LBM), including fibrotic and connective tissue, water, and organs. However, neither DXA nor CT directly quantifies total body muscle mass and both methods expose patients to radiation. Safe and non-invasive methods to assess muscle mass will contribute to our understanding of the mechanisms by which muscle loss may affect morbidity and mortality after cancer and enhance interventions such as physical activity that target muscle mass in cancer patients. To this end, for the first time in cancer patients, the proposed study will evaluate the associations of a direct and non-invasive method to assess total body muscle mass with outcomes. Deuterated creatine dilution (d3-creatine) estimates total creatine pool size, and thus muscle mass, using an oral dose of d3-creatine and measuring d3-creatinine enrichment in a single, spot-urine sample a few days later. Since creatine is located within the contractile components of the sarcomere, d3-creatine dilution provides a measure of functional muscle mass. This study will measure d3-creatine muscle mass in 90 colon cancer patients participating in a randomized controlled trial of resistance training during chemotherapy in which CT CSA and DXA LBM are already being collected. We will test whether d3-creatine muscle mass changes in response to resistance training and examine whether d3- creatine muscle mass is associated functional, metabolic, inflammatory and chemotherapy outcomes. In addition, we will compare the strength of the associations with outcomes found with d3-creatine muscle mass to those with CT CSA and/or DXA LBM. If d3-creatine muscle mass in cancer patients is predictive of strength, function, chemotoxicity and cancer-related biomarkers, then d3-creatine dilution will be a useful tool for research on the role of muscle mass and physical activity interventions in cancer patients. In the future, informed by the evidence generated in this study, the simple d3-creatine dilution test might someday be used clinically to identify cancer patients with low muscle mass for interventions to mitigate chemotoxicity, cardiometabolic risk, functional impairment and mortality.

抽象的 结直肠癌（CRC）是美国第四常见的癌症。在临床上使用 获得的计算机断层扫描（CT）扫描以测量肌肉横断面区域（CSA），流行率 非转移性CRC患者的低肌肉估计为42％。低CT CSA与 超过2倍以上的趋化风险增加了，手术并发症的风险增加了26％，46％ CRC特异性死亡的风险增加。但是，使用CT来估计肌肉质量是限制的，因为 CT并不是所有癌症的护理标准，通常仅限于一个解剖区域，无法区分 在收缩肌肉蛋白和肌肉筋膜中的其他组织之间。替代方案包括双能X射线 吸收法（DXA），测量所有瘦体重（LBM），包括纤维化组织和结缔组织， 水和器官。但是，DXA和CT均未直接量化全身肌肉质量和两种方法 暴露于辐射患者。评估肌肉质量的安全和非侵入性方法将有助于我们 了解癌症后肌肉损失可能影响发病率和死亡率的机制和 增强干预措施，例如靶向癌症患者肌肉质量的体育活动。为此， 在癌症患者中，第一次研究将评估直接和非侵入性的关联 用结局评估全身肌肉质量的方法。氘化肌酸稀释（D3-receatine）估计值 肌酸池的总大小，因此使用口服d3-熟食剂量并测量D3-retreatinine 几天后，在单个点尿样品中富集。由于肌酸位于收缩物中 肌膜的成分，D3-熟食稀释提供了功能性肌肉质量的量度。这项研究 将测量参加一项随机对照试验的90名结肠癌患者的D3-酸性肌肉质量 CT CSA和DXA LBM的化学疗法期间的抗性训练。我们 将测试D3-绘制的肌肉质量是否会因抗性训练而发生变化，并检查D3-是否是否 肌酸肌肉质量是相关的功能，代谢，炎症和化学疗法的结果。在 此外，我们将将关联的强度与与D3-熟食肌肉质量发现的结果进行比较 对于患有CT CSA和/或DXA LBM的人。如果癌症患者的D3-摄入的肌肉量可以预测强度，则 功能，趋化毒性和与癌症相关的生物标志物，那么D3-熟食稀释将是有用的工具 研究肌肉质量和体育锻炼干预措施在癌症患者中的作用。将来， 在本研究中产生的证据中得知，可能有一天可以使用简单的D3熟食测试 临床上以识别肌肉质量低的癌症患者，以减轻趋化性， 心脏代谢风险，功能障碍和死亡率。