# A SkeleTal muscle Recovery Intervention with Dietary protein in Heart Failure (ASTRID-HF)

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $322,554

## Abstract

PROJECT SUMMARY
Skeletal muscle wasting and catabolic weight loss are highly prevalent among patients with heart failure with
reduced ejection fraction (HFrEF) and are independently associated with increased mortality. As many as half
of patients with advanced HFrEF have dual X-ray absorptiometry (DXA) evidence of significant muscle mass
loss. It currently unknown whether protein supplementation can reverse muscle loss and improve physical
function or survival for affected patients. The deranged systemic metabolism thought to accompany skeletal
muscle wasting in patients with HFrEF may also be a source of potential therapeutic intervention to improve
both muscle mass and survival. We have observed significant gains in skeletal muscle mass in the first 3-6
months after implantation of a left ventricular assist device, which treats the advanced HFrEF syndrome and
helps to normalize the deranged systemic metabolism. In the proposed project, we will perform a randomized
controlled trial of oral protein supplementation to determine its effectiveness in achieving clinically meaningful
increases in muscle mass muscle. We also plan to expand knowledge specific to HFrEF of two of the main
catabolic pathways thought to drive muscle wasting downstream from growth-differentiation factor 15 (GDF-15)
and the activin type IIA/IIB receptor (ActRII). Successful completion of the proposed Aims will facilitate our
long-term goal to develop nutritional and pharmacological interventions that prevent or reverse skeletal muscle
wasting and consequently improve physical functioning and survival for patients with HFrEF. Based on our
preliminary and published data, we propose to test the innovative hypothesis that skeletal muscle wasting in
HFrEF is promoted by neurohumoral activation of catabolic metabolism, including GDF-15 and ActRII
pathways, and can be at least partially reversed by enhanced dietary protein intake. We will test this
hypothesis by enrolling 140 adults with HFrEF for a cross-sectional assessment of GDF-15 and ActRII
pathways (Aim 1) and skeletal mass response to protein supplementation in a mechanistic clinical trial (Aim 2).
Aim 1 will determine whether GDF-15 of ActRII inhibition may be future therapies for patients with severe
muscle wasting that cannot be overcome by nutritional strategies. Aim 2 will define whether 30 gram/day
supplemental dietary protein for 6 months can increase dual X-ray absorptiometry (DXA) appendicular lean
maa (ALM). Successful completion of these aims will establish if dietary protein supplementation is indicated
in the clinical care of patients with HFrEF and catabolic weight loss and provide a platform for future studies of
adjunctive therapies of GDF-15 neutralization or activin A inhibition. Developing innovative interventions to
promote skeletal muscle mass and physical function for patients with HFrEF aligns well with the NHLBI’s
objective to develop novel therapeutic approaches for treating heart diseases and improv...

## Key facts

- **NIH application ID:** 11125060
- **Project number:** 7R01HL167113-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Amanda Ruth Vest
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $322,554
- **Award type:** 7
- **Project period:** 2023-03-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11125060

## Citation

> US National Institutes of Health, RePORTER application 11125060, A SkeleTal muscle Recovery Intervention with Dietary protein in Heart Failure (ASTRID-HF) (7R01HL167113-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11125060. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*