# Pre-clinical study for the use of D3-Creatine as a biomarker in cachexia clinical trials

> **NIH VA I21** · EDWARD HINES JR VA HOSPITAL · 2024 · —

## Abstract

Veterans with cancer are susceptible to muscle wasting disorders including both cachexia (chronic
disease related) and sarcopenia (age related). The cumulative effect of this muscle wasting is both poor
response to cancer treatments and high risk of physical disability. Unfortunately, clinical trials for cancer related
cachexia have encountered several barriers, including lack of precise diagnosis and classification of true
muscle wasting in cancer patients. Current approaches to cachexia diagnosis include body weight and indirect
body composition measures via imaging modalities. However, these approaches are flawed, lack specificity to
muscle, and do not correlate well with physical functional outcomes. D3-creatine (D3-Cr) has recently emerged
as novel biomarker of functional skeletal muscle mass and correlates well with muscle and functional
outcomes in patients with age-related sarcopenia. Thus, D3-creatine has been suggested as a power tool for
estimating muscle mass for future clinical trials, including in cancer patients. However, D3-creatine has not
been specifically tested in the context of cancer muscle wasting, and others have postulated that the
relationship between D3-creatine and total muscle mass is confounded by muscle wasting pathology, including
cachexia and sarcopenia. Further study of D3-creatine is needed at the pre-clinical level before it can be
applied broadly in the cancer population.
 The major scientific goal in this study is to determine the specific utility of D3-Cr in predicting
muscle wasting and function in the context of cachexia, sarcopenia, and both during cancer. Using our
novel longitudinal pre-clinical mouse model of cancer-associated cachexia, in Aim 1, we will compare D3-Cr
levels in mature animals (20 weeks old) with and without cancer cachexia. We will then correlate D3-Cr levels
with physiologic cross-sectional area (PCSA) of an array of lower extremity muscles as well as physical
function. Function will be assessed using grip strength, treadmill time to fatigue, and maze-based assays for
assessing gait speed and cognitive function. We hypothesize that D3-Cr levels will strongly correlate with
PCSA and physical function measures in cancer animals. In Aim 2, we will assess D3-Cr levels, PCSA, and
physical function in aged animals (90 weeks old) with and without cancer cachexia. We again hypothesize that
D3-Cr levels will strongly correlate with PCSA and physical function measures in aged cancer animals.
However, we also hypothesize that in a two-way ANOVA of cancer and age, that there will be a significant
association between D3-CR and the interaction of these two variables.
 By completing this pre-clinical work, we will establish the specific pathologic conditions related to
cancer in which D3-Cr may be used to predict muscle wasting. More directed future clinical studies can then be
designed for the application of D3-Cr as a biomarker of cancer related muscle wasting.

## Key facts

- **NIH application ID:** 10916607
- **Project number:** 1I21RX005146-01
- **Recipient organization:** EDWARD HINES JR VA HOSPITAL
- **Principal Investigator:** Richard L. Lieber
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916607

## Citation

> US National Institutes of Health, RePORTER application 10916607, Pre-clinical study for the use of D3-Creatine as a biomarker in cachexia clinical trials (1I21RX005146-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10916607. Licensed CC0.

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