Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease

The Role of Phosphodiesterase Inhibitors in CF Lung Disease

The purpose of this study is to determine whether sildenafil can decrease inflammation in CF lung disease.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: sildenafil

Detailed Description

This study is an open-label study that examines the use of sildenafil (Revatio) in clinically stable patients with mild to moderate CF lung disease. The length of participation for each subject will be approximately 10 weeks, and will consist of a screening visit, a study visit for initiation of study drug if subject qualifies, interim visits to escalate drug dose, obtain drug levels, review concomitant medications and assess side effects, a visit at the end of the therapy period (to reassess inflammatory markers, laboratory studies and side effects,) and a follow-up assessment 2 weeks after subject completion.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of CF based on the following criteria:

  • Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or
  • Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
• Male or female patients ≥ 12 years of age
• FEV1 ≥ 50% predicted (Knudson) 31
• Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit
• Ability to reproducibly perform spirometry (according to ATS criteria)
• Ability to produce at least 1mL of sputum spontaneously, or be willing to undergo sputum induction
• Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
• Chronic bacterial colonization (3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization)

Exclusion Criteria:

• History of hypersensitivity to sildenafil
• Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
• Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study
• Daily use of systemic corticosteroids and/or NSAIDs within 4 weeks of the study or as needed use within 72 hours prior to the screening visit
• History of significant hepatic (SGOT or SGPT > 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure >55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine >1.8 mg/dL.)
• Inability to swallow pills
• Previous lung transplantation
• Use of concomitant nitrates, α-blocker, or Ca channel blocker
• Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin)
• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data
• Weight less than 40 kg
• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening
• Resting room air oxygen saturation <93%
• History of migraines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pilot study of systemic sildenafil administration to people with cystic fibrosis; This is a study of sildenafil administration to patients with mild to moderate cystic fibrosis (CF). All subjects will receive oral sildenafil three times per day during the study. Study endpoints will be measured before the treatment period and at the end of the treatment period to evaluate safety, tolerability, pharmacokinetics in people with CF, and surrogate markers of pulmonary function.

Drug: sildenafil; Sildenafil will be given 20mg po tid for 1 week, and then will be give 40mg po tid for 5 weeks.; Other Names: Revatio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sputum Elastase Activity	Exploratory analysis for efficacy of sildenafil on sputum biomarkers of inflammation, including sputum elastase. This measure will indicate whether sildenafil will increase or decrease sputum elastase activity.	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Exhaled Breath Condensate pH	Endogenous airway acidification can be assessed by measuring pH in exhaled breath condensate, a non-invasive measure of response to therapy. This measure will indicate whether sildenafil will improve, worsen, or cause no change in exhaled breath condensate pH.	Baseline and 6 weeks
Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain, Average Unit Change From Baseline to 6 Weeks is Reported	The CFQ-R is designed to measure CF-specific patient-reported health-related quality of life. It is a validated CF-specific quality of life measure. The CFQ-R Respiratory domain score (scale 0-100 with higher scores indicating better quality of life). This measure will indicate whether sildenafil will improve, worsen, or cause no change in the CFQ-R respiratory domain scores from baseline at 6 weeks.	6 weeks

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jennifer L Taylor-Cousar, MD, National Jewish Health

Publications and helpful links

General Publications

• Poschet JF, Timmins GS, Taylor-Cousar JL, Ornatowski W, Fazio J, Perkett E, Wilson KR, Yu HD, de Jonge HR, Deretic V. Pharmacological modulation of cGMP levels by phosphodiesterase 5 inhibitors as a therapeutic strategy for treatment of respiratory pathology in cystic fibrosis. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L712-9. doi: 10.1152/ajplung.00314.2006. Epub 2007 Jun 22.
• Taylor-Cousar JL, Wiley C, Felton LA, St Clair C, Jones M, Curran-Everett D, Poch K, Nichols DP, Solomon GM, Saavedra MT, Accurso FJ, Nick JA. Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease. J Cyst Fibros. 2015 Mar;14(2):228-36. doi: 10.1016/j.jcf.2014.10.006. Epub 2014 Nov 13.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2008
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 14, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimated): April 16, 2008

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: inflammation; cystic fibrosis; pH; EBC; phosphodiesterase inhibitors; sputum biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Inflammation; Cystic Fibrosis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Purines; Sulfonamides; Sulfones; Piperazines; Sildenafil Citrate
• Other Study ID Numbers: 851R14-8510M3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO