NCT01132482

Effects of Sildenafil on CFTR-dependent Ion Transport Activity

Phase II Study of the Effects of Sildenafil on CFTR-dependent Ion Transport Activity

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: National Jewish Health · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Cystic Fibrosis

Interventions

Type	Name	Description
DRUG	Sildenafil	During the course of the study, patients will receive 4 weeks of therapy: 28 days of placebo orally t.i.d. or 28 days of days of sildenafil orally t.i.d. Dosing of sildenafil will be escalated after the first week (20 mg orally t.i.d for the first week, then subjects will take 40 mg orally t.i.d. for 3 weeks). Patients not tolerating dose escalation will be discontinued from the study.
DRUG	Placebo	Patients receiving placebo will have sham dose escalation to maintain blinding.

Timeline

• Start date: 2015-10-01
• Primary completion: 2017-05-01
• Completion: 2017-05-01
• First posted: 2010-05-28
• Last updated: 2019-03-19
• Results posted: 2019-02-26

Locations

1 site across 1 country: United States