# Collaborative Clinical Research in Nonalcoholic Steatohepatitis

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $235,419

## Abstract

PROJECT SUMMARY
This application is submitted in response to the RFA-DK-18-505 which is a limited competition opportunity to
continue the support for the clinical centers of the NASH Clinical Research Network (NASH CRN). Although
significant progress has been made in our understanding of this disease, numerous clinically important
knowledge gaps remain which will be addressed by the NASH CRN during the next funding cycle. To meet the
research objectives of the RFA-DK-18-505, we propose the following specific aims during the next funding
period: Specific Aim 1: To successfully complete the following ongoing multicenter studies: (a) NAFLD
Database 2, a longitudinal database of adults (n=2240) and children (n=949) with biopsy proven NAFLD, (b)
STOP-NAFLD (n=110), a randomized, placebo-controlled, double-blind trial of losartan in children with biopsy
proven NAFLD, and (c) VANISH (n=90), a randomized, placebo-controlled, double-blind trial of vatiquinone in
adults with histologically characterized NAFLD; Specific Aim 2: To successfully complete ongoing ancillary
and translational studies initiated during the current funding period by the IU Clinical Center; Specific Aim 3:
Our central hypothesis is that FADS1 genetic variation is highly important for pediatric NAFLD. (A) To
investigate the relationship between FADS1 genetic variation and liver histology in children with biopsy proven
NAFLD. In more than 1,200 children with biopsy-proven NAFLD enrolled at multiple clinical centers in the
United States, we will examine the genotype-phenotype correlation between FADS1 haplotype and liver
histology in pediatric NAFLD. (B) To test the hypothesis that FADS1 genotype predicts the response to
EPA/DHA treatment in children with NAFLD. We will test this hypothesis by conducting a clinical study in which
25 children with NAFLD who are homozygote for FADS1 low-activity haplotype (haplotype A/A18) and 25
children with NAFLD who are homozygote for normal-activity haplotype (haplotype D/D18) will receive fish oil
(2-3 grams weight based) orally every day for 16 weeks. The EPA/DHA enrichment of erythrocytes following
fish oil supplementation is the pharmacodynamic endpoint whereas changes in hepatic fat and serum
aminotransferases are the efficacy endpoints. Specific Aim 4: To evaluate a novel PPAR α/γ agonist,
saroglitazar, in adults with NASH. Saroglitazar is a highly attractive agent for further testing due to strong
rationale for PPARα/γ agonism in improving NASH and robust preclinical and early clinical and safety data. In
this randomized controlled trial, 160 adults with NASH meeting predefined eligibility will receive either
saroglitazar (4 mg orally daily) or placebo for 72 weeks. The primary efficacy endpoint is improvement in
centrally reviewed liver histology, defined as a decrease in NAFLD activity score (NAS) by at least 2 points
without worsening of fibrosis.

## Key facts

- **NIH application ID:** 10450715
- **Project number:** 5U01DK061737-21
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** NAGA P CHALASANI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,419
- **Award type:** 5
- **Project period:** 2002-05-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450715

## Citation

> US National Institutes of Health, RePORTER application 10450715, Collaborative Clinical Research in Nonalcoholic Steatohepatitis (5U01DK061737-21). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10450715. Licensed CC0.

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