Sildenafil for Chronic Obstructive Pulmonary Disease

• 6 Minute Walk Distance [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  The distance a subject walked within 6 minutes was measured and documented.
• VO2 Peak (Oxygen Consumption at Peak Exercise) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Oxygen consumption at peak exercise was measured at scheduled timepoints during treatment periods 1 and 3.

• Pulmonary Function FVC (Forced Vital Capacity) [ Time Frame: Period 1 (4 weeks) ] [ Designated as safety issue: No ]
  Data to calculate results for FVC was based on Period 1.
• Forced Expiratory Volume in the First Second (FEV1 ) [ Time Frame: Period 1 ( 4 weeks) ] [ Designated as safety issue: No ]
  The volume of air exhaled in the first second. Data to calculate results for FEV1 was based on Period 1 only.
• Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Participants were asked to scale the breathlessness felt at the end of 6MWT from 0 to 10, with 0 being the least discomfort and 10 being the most discomfort in breathing.
• Diffusing Capacity of Carbon Monoxide (DLCO) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Carbon Monoxide Diffusing Capacity was measured on the same days as the pulmonary function tests.
• Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Partial pressure of carbon dioxide in ABG performed breathing room air at rest.
• Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Partial Pressure of Oxygen in ABG breathing room air at rest.
• A-a Gradient (Alveolar-arterial Gradient) [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  A-a gradient was measured with ABG breathing room air at rest.
• Oxygen Pulse [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  Oxygen pulse during Cardiopulmonary exercise test at peak exercise.
• O2 Saturation at Peak Exercise [ Time Frame: Period 1 and Period 3 ( within 8 weeks) ] [ Designated as safety issue: No ]
  O2 Saturation at Peak Exercise measured during the Cardiopulmonary exercise test.

• Pulmonary Function
• Quality of Life
• Shortness of breath score

The purpose of this study is to determine if sildenafil improves the exercise capacity and lung function of patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) suffer from impaired exercise capacity and quality-of-life, largely related to shortness of breath. Many of the therapies currently available for COPD are aimed at improving these factors. Exercise capacity is limited in part by high blood pressure in the blood vessels in the lungs. Sildenafil, also known as Viagra, is an FDA-approved therapy for male erectile dysfunction. One of its effects is to relax (or open) the lung vessels, thereby lowering the blood pressure in the lungs. We hypothesize that sildenafil will result in an improvement in exercise capacity, quality-of-life, and shortness of breath.

Enrolled subjects will receive sildenafil or placebo for 4 weeks followed by exercise tests, breathing tests, and administration of quality-of-life questionnaires. Subjects will then receive placebo or sildenafil (whichever one they did not receive for the first 4 weeks) for another 4 weeks, followed by the same testing.

• Pulmonary Disease, Chronic Obstructive
• Emphysema

• Drug: sildenafil citrate
  sildenafil citrate 25 mg by mouth thrice daily (po tid)
• Drug: Placebo
  25 mg po tid

• Active Comparator: Sildenafil / Placebo
  Sildenafil first, followed by washout, followed by placebo
  Interventions:

  • Drug: sildenafil citrate
  • Drug: Placebo
• Placebo Comparator: Placebo / Sildenafil
  Placebo first, followed by washout, followed by Sildenafil
  Interventions:

  • Drug: sildenafil citrate
  • Drug: Placebo

Inclusion Criteria:

• Clinical diagnosis of chronic obstructive pulmonary disease (COPD) or emphysema
• FEV1/FVC ratio < 70%
• FEV1 < 80%
• Stable medication regimen

Exclusion Criteria:

• COPD exacerbation or hospitalization in the past 3 months
• Heart disease
• Contraindication to sildenafil
• Unrelated lung disease
• Inability to walk or pedal on a stationary bike
• Pregnancy or breast-feeding
• Pulmonary hypertension at rest