The overall objective of this proposal is to discover novel therapy for the treatment of IPF. We propose two projects. The first project aims to determine the safety and efficacy of sirolimus combined with interferon gamma-1b (IFN-y lb) in 138 patients with idiopathic pulmonary fibrosis (IPF). We propose a two-year multi-center, randomized, double-blinded, controlled study of sirolimus plus IFN-y lb compared to IFN-y lb plus placebo in patients with IPF. Eligible patients will be randomly assigned, in a 2:1 ratio, to receive sirolimus plus IFN-y lb versus IFN-y lb plus placebo, respectively. Randomization will use a randomized permuted block design stratified by clinic with changing block sizes. The primary efficacy outcome is the 6-minute walk distance (6MWD). Secondary efficacy endpoints include pulmonary function, gas exchange, and quality of life (QOL). We hypothesize that patients with mild to moderate IPF (FVC >55% and DLCO >30% of predicted) will demonstrate stabilization or improvement in 6MWD over 96 weeks of treatment with combined therapy. The control group will be expected to demonstrate deterioration in 6MWD. The second project aims to determine the safety and efficacy of sildenafil in 100 patients with IPF and moderate pulmonary arterial hypertension (PAH;defined as meaning pulmonary arterial pressure >30 mm Hg at rest). We propose a 12-week multi-center, randomized, double-blinded, controlled study of sildenafil compared placebo in patients with IPF and PAH. Eligible patients will be equally randomized (1:1) into active or placebo groups. Randomization will use the permuted block design with stratification by clinic. The primary efficacy outcome is the 6MWD. Secondary efficacy endpoints include gas exchange and quality of life (QOL). We anticipate an improvement in 6MWD in patients who receive sildenafil compared to those who receive placebo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL080411-05
Application #
7616765
Study Section
Special Emphasis Panel (ZHL1-CSR-M (F1))
Program Officer
Reynolds, Herbert Y
Project Start
2005-05-01
Project End
2012-04-30
Budget Start
2009-05-01
Budget End
2012-04-30
Support Year
5
Fiscal Year
2009
Total Cost
$197,025
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Durheim, Michael T; Collard, Harold R; Roberts, Rhonda S et al. (2015) Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials. Lancet Respir Med 3:388-96
Idiopathic Pulmonary Fibrosis Clinical Research Network; Martinez, Fernando J; de Andrade, Joao A et al. (2014) Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 370:2093-101
Swigris, Jeffrey J; Streiner, David L; Brown, Kevin K et al. (2014) Assessing exertional dyspnea in patients with idiopathic pulmonary fibrosis. Respir Med 108:181-8
Collard, Harold R; Brown, Kevin K; Martinez, Fernando J et al. (2014) Study design implications of death and hospitalization as end points in idiopathic pulmonary fibrosis. Chest 146:1256-1262
Han, MeiLan K; Bach, David S; Hagan, Peter G et al. (2013) Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest 143:1699-1708
Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu, Ganesh; Anstrom, Kevin J et al. (2012) Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 366:1968-77
Noth, Imre; Anstrom, Kevin J; Calvert, Sara Bristol et al. (2012) A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186:88-95
Swigris, Jeffrey J; Han, Meilan; Vij, Rekha et al. (2012) The UCSD shortness of breath questionnaire has longitudinal construct validity in idiopathic pulmonary fibrosis. Respir Med 106:1447-55
(2010) The IPFnet Strategy: Creating a comprehensive approach in the treatment of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 181:527-8

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