Effects of Sildenafil on CFTR-dependent Ion Transport Activity

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2017-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT00659529

Cystic Fibrosis

COMPLETED PHASE1/PHASE2

Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe CF

NCT02626182

Cystic Fibrosis

COMPLETED PHASE1/PHASE2

Sildenafil Trial in Children and Young Adults With CF

NCT01194232

Cystic Fibrosis With Mild to Moderate Lung Disease CMRI of Lung Perfusion Lung Perfusion +1 more

WITHDRAWN PHASE1/PHASE2

Blood Flow and Vascular Function in Cystic Fibrosis

NCT02057458

Cystic Fibrosis

COMPLETED PHASE2

Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis

NCT00570349

Cystic Fibrosis

COMPLETED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cystic Fibrosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sildenafil

Subjects will receive escalating doses of sildenafil

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

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.

Placebo

During the placebo arm, subjects receiving placebo will have sham dose escalation to maintain blinding.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Patients receiving placebo will have sham dose escalation to maintain blinding.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Placebo

Patients receiving placebo will have sham dose escalation to maintain blinding.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Revatio

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and genotype with two F508del CFTR mutations, and accompanied by one or more clinical features consistent with the CF phenotype
2. Male or female subjects ≥ 18 years of age
3. FEV1 ≥ 50% predicted (Hankinson)
4. 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
5. Ability to reproducibly perform spirometry (according to ATS criteria)
6. Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
7. Willing and able to perform nasal potential difference testing
8. No changes in use of nasal medications within 2 weeks of screening visit
9. If on Orkambi, has been on stable Orkambi dose for at least 4 weeks at day 1.

Exclusion Criteria

1. History of hypersensitivity to sildenafil
2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
3. 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
4. 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.)
5. Inability to swallow pills
6. Previous lung transplantation
7. Use of concomitant nitrates, α-blocker, or Ca channel blocker
8. Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin, verapamil)
9. 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
10. Weight less than 40 kg
11. History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening
12. History of nasal disease or nasal surgery that would, in the opinion of the investigator, impede accurate measurements of NPD
13. Use of anticoagulant medication (e.g. heparin, coumadin)
14. Resting room air oxygen saturation \<93%
15. Use of nighttime oxygen

15\) History of migraine headaches 16) Baseline BP of \< 90/50 mm Hg

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No