Sildenafil for Chronic Obstructive Pulmonary Disease

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

Detailed Description
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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.

Official Title
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A Double-blind, Placebo-controlled, Crossover Study of Sildenafil in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive, Emphysema

Intervention / Treatment
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* Drug: sildenafil citrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil / Placebo<br>Sildenafil first, followed by washout, followed by placebo | Drug: sildenafil citrate<br>* sildenafil citrate 25 mg by mouth thrice daily (po tid)<br>Drug: Placebo<br>* 25 mg po tid<br>|
| Placebo Comparator: Placebo / Sildenafil<br>Placebo first, followed by washout, followed by Sildenafil | Drug: sildenafil citrate<br>* sildenafil citrate 25 mg by mouth thrice daily (po tid)<br>Drug: Placebo<br>* 25 mg po tid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Distance | The distance a subject walked within 6 minutes was measured and documented. | Period 1 and Period 3 ( within 8 weeks) | 
| VO2 Peak (Oxygen Consumption at Peak Exercise) | Oxygen consumption at peak exercise was measured at scheduled timepoints during treatment periods 1 and 3. | Period 1 and Period 3 ( within 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Function FVC (Forced Vital Capacity) | Data to calculate results for FVC was based on Period 1. | Period 1 (4 weeks) | 
| Forced Expiratory Volume in the First Second (FEV1 ) | The volume of air exhaled in the first second. Data to calculate results for FEV1 was based on Period 1 only. | Period 1 ( 4 weeks) | 
| Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT) | 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. | Period 1 and Period 3 ( within 8 weeks) | 
| Diffusing Capacity of Carbon Monoxide (DLCO) | Carbon Monoxide Diffusing Capacity was measured on the same days as the pulmonary function tests. | Period 1 and Period 3 ( within 8 weeks) | 
| Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG) | Partial pressure of carbon dioxide in ABG performed breathing room air at rest. | Period 1 and Period 3 ( within 8 weeks) | 
| Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG) | Partial Pressure of Oxygen in ABG breathing room air at rest. | Period 1 and Period 3 ( within 8 weeks) | 
| A-a Gradient (Alveolar-arterial Gradient) | A-a gradient was measured with ABG breathing room air at rest. | Period 1 and Period 3 ( within 8 weeks) | 
| Oxygen Pulse | Oxygen pulse during Cardiopulmonary exercise test at peak exercise. | Period 1 and Period 3 ( within 8 weeks) | 
| O2 Saturation at Peak Exercise | O2 Saturation at Peak Exercise measured during the Cardiopulmonary exercise test. | Period 1 and Period 3 ( within 8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Emphysema, Phosphodiesterase inhibitors, Sildenafil, Exercise testing, Quality of life