1/2 prospective treatment efficacy in IPF uslng genotype for NAC selection (precisions) trial and molecular endophenotyping in idiopathic pulmonary fibrosis and interstitial lung diseases study

Active Cooperative Agreement Awarded Last action

Award ID
UH3HL145266
Recipient
Awarding agency
Obligated
$35,668,686

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 93% complete
Originally
Funding
  • $32,867,782.40 Federal
  • $2,800,903.20 Non-federal
Place of performance
Worcester, MA 01655, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Despite being the most frequent and deadly of the interstitial lung diseases (ILD), idiopathic pulmonary fibrosis (IPF) remains challenging to diagnose and treat. The diagnostic process for IPF relies on subjective interpretations of clinical data while current antifibrotic therapies employ a "one size fits all" paradigm. Members of our team have been at the forefront of developing `omics approaches to diagnose and define prognosis in ilds. Importantly, we identified the first pharmacogenomic interaction suggesting that IPF patients with tollip RS3750920 t/t genotype strongly benefited from NAC. There is a critical need for molecular classifications that define IPF, thus allowing precision-based management. Our long-term goals are to move ILD diagnosis and therapy into the "ERA of precision medicine." in a highly innovative approach we have partnered with the pulmonary fibrosis foundation (PFF) clinical care network (CCN) and registry. This group has recruited ILD patients who have provided extensive baseline phenotypic and longitudinal outcome data, biological samples and have consented to be RE-contacted for future research. Our overall objective is to efficiently conduct a novel, precision genotype-based trial in IPF while leveraging the CCN and its unique biospecimen collection to characterize a broad range of ilds molecularly and identify genetic variants of IPF risk. To address our goal of precision-based ILD management, we will complete three complementary specific aims. In aim 1 we will determine if NAC is an effective treatment in IPF patients characterized by a precision genotype approach. In partnership with the PFF, we will identify PFF registry subjects with the tollip t/t genotype to begin randomizing 200 IPF patients followed by enrolling new subjects at the same clinical sites to receive NAC or placebo in a double-blind fashion. This study, the "prospective treatment efficacy in IPF using genotype for NAC selection (precisions)" trial, will document the benefits of an innovative "precision" genotype-specific study design of a well-tolerated and inexpensive therapy. In aim 2 we will distinguish IPF from non-IPF ilds using unbiased combinations of blood transcriptomics and proteomics. We propose to conduct RNA-SEQ and proteomics to characterize gene expression and protein biomarkers on the entire PFF registry cohort. We will define "signatures" for distinguishing IPF from non-IPF ilds. Our unbiased approaches to `omics traits will be integrated to reveal `omics risk scores that define individual diseases, predict disease course, and response to therapy. In aim 3 we will identify genetic variants playing a role in IPF risk. We will conduct whole genome sequencing of the entire PFF cohort to detect novel genetic associations for IPF and ILD risk. With sufficient power, we will assess both common and rare/infrequent variants in comparison to ethnically matched UN-afflicted cases, and between ILD cohorts to meet our objective. This will establish the largest collection of its kind and establish quantitative trait loci for all `omics' data. The results of our proposed experiments will move ILD management, and IPF therapy, in particular, into the precision medicine ERA.

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Subawards

Subrecipient Amount Awarded
Pulmonary Fibrosis Foundation The Pulmonary Fibrosis Foundation (PFF) will support the PRECISIONS study in project planning and clinical trial time periods. A Senior Medical Advisor for… $34,771
Regents Of The University Of Michigan Dr. Spino and the University of Michigan will be the Data Coordination Center (DCC) and will engage with subcontracts with 25 clinical sites and will monitor… $41,750
Rector & Visitors Of The University Of Virginia In addition to participating as an enrolling center for the trial, the University of Virginia will lead several aspects of the CCC project. Dr. Noth is co-PI… $915,651
University Of Alabama At Birmingham The University of The University of Alabama at Birmingham (Dr. James Michael Wells) are pleased to assist as a subcontractor of UMass Chan Medical School with… $19,104
Pulmonary Fibrosis Foundation Dr. Cosgrove will facilitate close interaction between the PRECISIONS investigators, the Pulmonary Fibrosis Foundation and members of the PFF Care Center… $245,535
Rector & Visitors Of The University Of Virginia In addition to participating as an enrolling center for the trial, the University of Virginia will lead several aspects of the CCC project. Dr. Noth is co-PI… $7,126,835
University Of California, LOS Angeles We have partnered with the University of California, LA, under the direction of Dr. Christopher Cooper, to provide oversight and home spirometry data analysis… $93,423
Regents Of The University Of Michigan Scope of Work: Dr. Lee will facilitate close interaction between the PRECISIONS investigators, the Pulmonary Fibrosis Foundation and members of the PFF Care… $190,842
University Of Washington $96,346

Quick answers

Who received award UH3HL145266?

UH3HL145266 was awarded to University Of Massachusetts Medical School by National Heart Lung and Blood Institute (National Institutes of Health) on September 1, 2020.

How much is award UH3HL145266 worth?

$35,668,686 has been obligated on UH3HL145266: $32,867,782 in federal funding and $2,800,903 in non-federal funding.

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