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

NCT00659529 | Completed Phase 1 Results DMC

• 1 other identifier: 851R14-8510M3
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; inflammation; pH; EBC; sputum biomarkers; phosphodiesterase inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

  6 weeks

Study Arms (1)

Pilot study of systemic sildenafil administration to people with cystic fibrosis

EXPERIMENTAL

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

Interventions

sildenafil DRUG

Sildenafil will be given 20mg po tid for 1 week, and then will be give 40mg po tid for 5 weeks.

Also known as: Revatio

Pilot study of systemic sildenafil administration to people with cystic fibrosis

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Jewish Health: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (2)

• 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.

  PMID: 17586695 BACKGROUND

• 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.

  PMID: 25466700 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Jennifer L. Taylor-Cousar, MD
• Organization: National Jewish Health

Taylor-CousarJ@NJHealth.org

(303) 270-2764

Study Officials

• Jennifer L Taylor-Cousar, MD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2008
• First Posted: April 16, 2008
• Study Start: August 1, 2008
• Primary Completion: August 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 14, 2026
• Results First Posted: May 2, 2014

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)