Official Title: “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 Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2010

This study is a placebo-controlled, double blind cross-over study of (sildenafil) Revatio® in clinically stable patients with mild to moderate CF lung disease. The length of participation for each subject will be approximately 14 weeks, and will consist of a screening visit, two in-patient study visits with initiation of study drug and/or placebo, two interim visits during therapy, two visits at end of each therapy period (to reassess inflammatory markers, pulmonary function, laboratory studies and side effects,) a 28-day washout period with coordinator phone call, and a follow-up assessment 2 weeks after subject completion.

Intervention(s) in this Clinical Trial

• Drug: sildenafil
  • Sildenafil or placebo will be given 20mg po tid for 28 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Placebo/sildenafil Subjects will be randomized to receive the following treatment sequence: placebo/sildenafil or sildenafil/placebo. A 28-day washout period will proceed entrance into the 2nd treatment sequence.
• Experimental: 2
  • Sildenafil/placebo Subjects will be randomized to receive the following treatment sequence: placebo/sildenafil or sildenafil/placebo. A 28-day washout period will proceed entrance into the 2nd treatment sequence.

Primary Measures

• Sputum IL-8 and elastase
  • Time Frame: Pre/post therapy
    Safety Issue?: No

Secondary Measures

• Exhaled breath condensate pH
  • Time Frame: Pre/post therapy
    Safety Issue?: No
• CFQ-R
  • Time Frame: Pre/post therapy
    Safety Issue?: No
• Serum sildenafil levels
  • Time Frame: Pre/during therapy
    Safety Issue?: No

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 ≥ 40% 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of New Mexico

Overall Clinical Trial Officials and Contacts

Jennifer L Taylor-Cousar, MD Principal Investigator University of New Mexico  

Overall Contact: Jolene Vigil, BA/BS 505-272-6955 jolvigil@salud.unm.edu

Information obtained from ClinicalTrials.gov on August 21, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00659529

Study ID Number: 851R14-8510M3

ClinicalTrials.gov Identifier: NCT00659529

Health Authority: United States: Institutional Review Board