Sildenafil Trial in Children and Young Adults With CF
Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.
Cystic Fibrosis With Mild to Moderate Lung Disease
CMRI of Lung Perfusion
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease|
- Increase pulmonary perfusion [ Time Frame: 8 week visit ] [ Designated as safety issue: No ]• Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;
- Improved lung function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Improved exercise performance as measured by the following variables:
- Ventilatory equivalent of O2 and CO2 (VEO2 and VECO2)
- Maximum oxygen consumption (VO2 max)
|Study Start Date:||August 2012|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
15 subjects will receive 8 week course of Sildenafil administered at a dose of 20 mg per dose three times per day.
8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.