# Precision Medicine for Nutrition in EDEN

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $119,250

## Abstract

PROJECT ABSTRACT
Nutrition is an essential component in the care of critically ill patients with acute respiratory distress syndrome
(ARDS) who are often limited in volitional intake and who incur new deficits in physical function secondary to
their illness. Despite well-characterized associations between inadequate nutrition and adverse outcomes,
large multicenter trials of specific nutrition strategies have failed to consistently demonstrate clinical benefit
with any particular approach. The landmark NHLBI-funded Early versus Delayed Enteral Nutrition [EDEN] trial
investigated low-level (trophic) versus full enteral feeds in 1000 patients and demonstrated increased
gastrointestinal complications with full enteral feeds without any clinical benefit. Subsequently, current
guidelines recommend low-level feeds for all ARDS patients, however, ARDS is increasingly recognized as a
heterogeneous disease and a one-size-fits-all approach may not be appropriate. An essential first step in
individualizing nutrition in ARDS is identifying the clinical and biologic variables that contribute to heterogeneity
of treatment effect whereby individuals or groups vary in response to treatment. Thus, the overall goal of this
proposal is to characterize differential responses to nutrition by leveraging data and biospecimens from the
EDEN trial. In Aim 1, this proposal will investigate whether ARDS subphenotypes differed in response to low-
level versus full enteral nutrition in EDEN. Recent studies have identified two distinct ARDS subphenotypes
that differ in prognosis, host response, and potentially in response to treatments. ARDS subphenotypes have
not been investigated with regards to nutrition. Thus, Aim 1 will perform biologic assays to facilitate ARDS
subphenotype identification and will test for differences by subphenotype in clinical outcomes, in intestinal
permeability, and in incretin hormones. When released at physiologic levels in response to enteral nutrients,
incretins have beneficial effects on insulin release and glucose metabolism, but when released at
supraphysiologic levels in response to intestinal inflammation, incretins may worsen tolerance to nutrition by
reducing gastric motility. Incretins are not well characterized in ARDS. In Aim 2, this proposal will use
computational approaches that directly model individual treatment effects based on patient covariates allowing
for investigations of treatment response that result from a complex interaction between baseline demographics,
severity of illness, endocrine hormones, and inflammation at an individual patient level. Successful completion
of the proposed Aims will provide new knowledge on biologic responses to nutrition strategies, identify
mechanisms that contribute to heterogeneity of treatment effect at an individual level, and provide direction for
the next generation of precision nutrition studies in ARDS.

## Key facts

- **NIH application ID:** 10814843
- **Project number:** 5R21HL168070-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Faraaz Ali Shah
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $119,250
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814843

## Citation

> US National Institutes of Health, RePORTER application 10814843, Precision Medicine for Nutrition in EDEN (5R21HL168070-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10814843. Licensed CC0.

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