Acute Effect of Sildenafil on Exercise Tolerance and Functional Capacity in COPD, IPF and Post Pneumonectomy Patients

• Pulmonary diseases are increasingly important causes of morbidity and mortality in the modern world.
• Sildenafil, an orally administered a phosphodiesterase type 5 (PDE-5) inhibitor, targets the nitric oxide (NO) pathway. The drug was first approved for the treatment of Pulmonary Arterial Hypertension (PAH) in 2005.
• The aim of the suggested study is to examine the acute effect of oral intake of sildenafil on exercise tolerance and functional capacity in Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis (IPF) and post Pneumonectomy patients.
• The investigators hypothesize that oral ingestion of sildenafil prior the exercise may enhance exercise tolerance and improve function in COPD, IPF and post Pneumonectomy patients.
• Patients and Methods:

Sixty chronic lung disease patients males and females (aged 30 to 90 years) 20 COPD (GOLD III-IV) [9, 39] , 20 IPF and 20 post Pneumonectomy patients will be recruit to this study.

• All subjects will carried out two maximal cardiopulmonary exercise tests (CPET) on bicycle ergometer in different days; 60 min after intake of placebo and 60 min after intake of 100 mg sildenafil (Pfizer, Sandwich, UK), in random order.
• In first meeting prior exercise test at rest standard pulmonary function test, diffusion of CO, TLC and RV will be measured. In addition, Doppler Echocardiography and blood samples for NT-proBNP will be taken prior and post each CPET.
• After 15-20 minute of passive recovery post exercise test all patients will perform 3 short functional tests including 6 minute walk test to assess functional capacity.

Study Overview

• Status: Unknown
• Conditions: Chronic Obstructive Pulmonary Disease; Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Sildenafil

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Pulmonary Institute, Rabin Medical Center, Beilinson Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with severe COPD GOLD stage III- IV, FEV1 30-50% or less of predicted values, greater shortness of breath, reduced exercise capacity, repeated excretions and\ or with chronic respiratory failure [9, 39].
2. IPF patients diagnosed essentially according to the American Thoracic and European Respiratory Societies (ATS-ERS) by clinical diagnostic criteria of: (a) High-resolution computed tomography (HRCT) demonstrating a pattern of "confident" or "possible" IPF (b) Abnormal pulmonary physiology with evidence of restriction and/or impaired gas exchange (can exist during exercise alone) (c) Exclusion of other known causes of interstitial lung disease (e.g.: connective tissue disease, environmental exposure,etc.)[31].
3. Patients post Pneumonectomy more than 6 month from the amputation surgery for any diagnosis (Cancer, Trauma, and Infection- Bronchiectasis).

Exclusion Criteria:

1. Patients with known sensitivity or contraindications to phosphodiesterase 5 (PDE-5) inhibitor therapies will be excluding from the study.
2. Thromboembolic disease will be excluded by pulmonary CT-angiography or perfusion scan.
3. Patients with a history of left-sided heart failure will be excluded.
4. Patients will also exclude if they are on regular treatment with nitrates or PDE-5 inhibitors (Sildenafil, Tadalafil, Vardenafil).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil	Drug: Sildenafil; Acute single dose of 100 mg of sildenafil. Oral intake in tablet form.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2 Peak		2-30 days between exercise tests
6 min walk test	Distance walked in 6 min test	2-30 days between exercise tests
Functional Tests	30 seconds chair stand test- number of repetitions in 30 sec; 8-ft-up-and -go (agility and coordination)- number of sec that takes to complete the task.	2-30 days between exercise tests

Secondary Outcome Measures

Outcome Measure	Time Frame
Pulmonary Arterial Pressure	2-30 days between exercise tests
NT-pro-BNP	2-30 days between exercise tests

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Mordechai R Kramer, M.D, Rabin Medical Center, Belinson Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): November 1, 2012
• Study Completion (Anticipated): September 1, 2013

Study Registration Dates

• First Submitted: May 2, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): November 15, 2012
• Last Update Submitted That Met QC Criteria: November 13, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: COPD; IPF; Post Pneumonectomy Patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: RMCBH116278 CTIL