Collaborative Clinical Research in Nonalcoholic Steatohepatitis

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The RFA-DK-23-515 is a limited competition notice of funding opportunity which invites applications from existing clinical centers of the NASH CRN for completing the active clinical trial and the adult and pediatric NAFLD database studies and to undertake scientifically meritorious ancillary studies and publications during the next funding period which is for three years. The Indiana University Clinical Center is a founding member of the NASH CRN which maintained its seamless integration between adult and pediatric investigators throughout the previous funding cycles and has made numerous important contributions to the mission of the NASH CRN. We propose the following specific aims to meet the goals of this RFA: Specific Aim # 1: To complete the (a) NAFLD Database3 study, a longitudinal observational study of adults (Adult DB3, n=1271 currently and recruiting) and children (pediatric DB3, n=263 currently and recruiting) with biopsy proven NAFLD who are undergoing extensive multidimensional characterization at baseline and annually and (b) Vitamin E Dosing Study (VEDS) clinical trial which is comparing 24 weeks of 200 IU, 400 IU, or 800 IU of oral vitamin E versus placebo in 200 adults with NAFLD and elevated alanine aminotransferase (ALT, ≥ 60 U/L). The primary end point is improvement in ALT at week 24 as compared to baseline ALT. Specific Aim # 2: To complete an ancillary study which aims to undertake a comprehensive interrogation of genomic and transcriptomic correlates of disease severity and outcomes of pediatric and adult NAFLD. In collaboration with an external partner, we have completed whole exome sequencing of the genomic DNA from 2,405 adults and 953 children and bulk RNAseq of liver samples obtained from 504 adults and 207 children with NAFLD. Specific Aim # 3: To initiate and complete a new proteomics ancillary study in collaboration with RGC in adults with NAFLD. Targeted proteomics analysis will be conducted using the Olink® proteomics platform at the RGC inhouse laboratory on baseline and serial serum samples collected from adults with NAFLD and NASH who participated in various longitudinal observational studies and clinical trials conducted by the NASH CRN. Specific Aim # 4: To robustly participate in all cross-consortia activities including participating and leading (where appropriate) steering committee, ancillary studies committee, genetic subcommittee, publications and presentations committee, and pediatric NAFLD committee activities.

Grant Number: 5U01DK061737-24
NIH Institute/Center: NIH
Principal Investigator: NAGA CHALASANI