Effects of Sildenafil on CFTR-dependent Ion Transport Activity
Status:
Completed
Trial end date:
2017-05-01
Target enrollment:
Participant gender:
Summary
Dehydrated airway surfaces resulting from sodium hyperabsorption and lack of chloride
secretion are critical to the pathology that leads to the morbidity and mortality from Cystic
Fibrosis (CF) lung disease. Previously published work in CF cell lines has demonstrated that
by increasing cGMP and restoring inhibition of ENaC, sodium hyperabsorption may be reversed
following administration of a phosphodiesterase inhibitor (PDEi,) such as sildenafil.
Additionally it has been shown in CF cell lines and animal models, that phosphodiesterase
inhibitors/analogues can enhance chloride secretion and/or correct surface localization of
ΔF508 CFTR. The goal of this project is to translate the results of this work from the
laboratory into a clinical trial in patients with CF using an FDA-approved therapy. The
Specific Aims of this project are to: 1) Evaluate the effect of systemically administered
phosphodiesterase inhibitors on ion transport in CF by measurement of Na+ and Cl- conductance
by NPD and Na+ and Cl- concentration in sweat utilizing pilocarpine iontophoresis 2) To
establish appropriate dosing of sildenafil in CF by performing a dose-escalation study during
which patients are carefully monitored for side effects, plasma sildenafil levels are
obtained and outcome measures are compared based on the dose of sildenafil administered. The
results of this study in conjunction with those from an ongoing study examining the role of
sildenafil as an anti-inflammatory in CF will aid in establishing safety, pharmacokinetics
and mechanism of action of sildenafil in the treatment of CF lung disease.