Medicines that decrease blood pressure in the lungs may help idiopathic pulmonary fibrosis (IPF) patients function better. This study will test whether sildenafil improves the ability to exercise in patients with pulmonary fibrosis of unknown cause.

Idiopathic pulmonary fibrosis (IPF) is recognized as a predominantly noninflammatory paradigm of lung fibrosis, characterized by heterogeneous myofibroblast proliferation (usual interstitial pneumonia [UIP]) and a poor clinical prognosis. To date no therapies have been demonstrated in well-designed, randomized, controlled trials (RCT) to favorably influence functional status or survival of IPF patients. The need for effective therapies for VA patients with IPF is thus obvious and urgent.

The overall goal of this VA Merit Review clinical research is to generate rigorous preliminary data for evaluation of a new and potentially effective therapy for IPF. The established, combined Miami Veterans Affairs Medical Center (VAMC) - University of Miami (UM) IPF program has participated productively in a number of clinical trials to assess new agents for the therapy of IPF (e.g., interferon gamma-lb, imatinib mesylate, etanercept, bosentan). Our program is uniquely qualified to enroll large numbers of IPF patients in clinical trials, because of its large metropolitan population base (>5,000,000 people) and extensive referral network throughout South and Central America. The Veteran population of South Florida (Dade, Broward and Monroe Counties) is approximately 236,000 (U.S. Census Bureau). Of that number 39% are 65 years of age or older, making them at high risk for IPF. Because of its large Veteran and civilian population base, international referral network and previous experience as a "high enrollment center" in IPF clinical trials, the Miami VAMC-UM IPF program is uniquely qualified to anticipate the role of a CSP lead center.

Our central hypothesis is that sildenafil, a vasodilator, will have a beneficial effect compared to placebo on disease progression, defined as a significant change in the 6-minute walk distance or dyspnea index, in patients with IPF.

Specifically, we will test effects of sildenafil on IPF patients' exercise tolerance and level of dyspnea in a double blind, randomized, placebo controlled (one to one assignment) pilot study. Upon completion of this trial, it will be possible to assess efficacy of sildenafil on progression of disease in IPF and possibly introduce this agent into translational practice. Our specific objectives are:

Specific Objectives 1: To assess the possible therapeutic benefit of a vasodilator, sildenafil, on exercise tolerance in IPF patients.

The working hypothesis is that, compared to placebo, sildenafil will favorably affect rate of decline from baseline in exercise capacity (6-minutes walk).

Specific Objective 2: To assess and compare changes from baseline in pre- and post-exercise dyspnea in sildenafil and placebo control groups.

The working hypothesis is that application of this agent will lead to more sustained exercise and a more favorable clinical outcome in addition to a decrease in the degree of limiting dyspnea after exercise.

The application of vasodilator therapy in IPF is unique in that it directly targets key pathophysiologic mechanisms of functional limitation: Increased pulmonary vascular resistance and dyspnea due to exercise. This novel approach will have a significant impact on field, because it promises both additional insight into mechanisms of disease and immediate therapeutic options.

Inclusion Criteria:

• Clinical diagnosis of IPF
• 40-85 years of age
• 6-minute walk distance 150-500 m
• FVC 40-90% predicted
• DLCO 30-90% predicted

Exclusion Criteria:

• Severe pulmonary hypertension
• Severe heart failure
• FEV1/FVC < 0.7

3 years

No additional follow up