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

Phase 1

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: sildenafil

Registration Number: NCT00659529

Lead Sponsor: National Jewish Health

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	sildenafil	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.

Primary Outcome Measures