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

Award Number: R01CA240394
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$5,039 )
2025	2023	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	4	5/13/2025	NON-COMPETING CONTINUATION	-$5,039
														Subtotal = -$5,039

Issue Date FY: 2023 ( Subtotal = $380,025 )
2023	2023	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	4	2/17/2023	NON-COMPETING CONTINUATION	$380,025
														Subtotal = $380,025

Issue Date FY: 2022 ( Subtotal = $379,209 )
2022	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	3	2/25/2022	NON-COMPETING CONTINUATION	$341,285
2022	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	001	3	4/22/2022	NON-COMPETING CONTINUATION	$37,924
														Subtotal = $379,209

Issue Date FY: 2021 ( Subtotal = $377,538 )
2021	2021	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	2	1/30/2021	NON-COMPETING CONTINUATION	$377,538
														Subtotal = $377,538

Issue Date FY: 2020 ( Subtotal = $381,231 )
2020	2020	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Cancer Cause and Prevention Research	000	1	1/22/2020	NEW	$381,231
														Subtotal = $381,231

Grand Total All Awards = $1,512,964

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

Award Number: R01CA240394

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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