Sildenafil Study to Treat Idiopathic Pulmonary Fibrosis
Condition: Alveolitis, Fibrosing; Fibrosis, Pulmonary; Hypertension, Pulmonary
MeSH terms: Hypertension, Pulmonary; Pulmonary Fibrosis; Hypertension; Fibrosis
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): sildenafil
Intervention type(s): Drug
Intervention description(s): Assessing the possible therapeutic benefit of sildenafil on exercise tolerance in IPF patients.
Other intervention name(s): Revatio
Intervention MeSH terms: Sildenafil Citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: alveolitis, fibrosing; exercise, aerobic; fibrosis, pulmonary; hypertension, pulmonary