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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

基本信息

批准号：
10337029
负责人：
Elizabeth Marjorie Cespedes Feliciano
金额：
$ 37.92万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10337029
关键词：
Abdomen Affect Aging Anatomy 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 Patients Performance Status Physical Function Physical Performance Physical activity Proxy Radiation Randomized Randomized Controlled Trials Recurrent disease 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 reduced muscle mass resistance exercise response standard of care strength training surgical risk tool treatment risk

项目摘要

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.

摘要