Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sildenafil
Sponsored by

About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis, inflammation, pH, EBC, sputum biomarkers, phosphodiesterase inhibitors
Eligibility Criteria
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
Sites / Locations
- National Jewish Health
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
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.
Outcomes
Primary Outcome Measures
Sputum Elastase
Secondary Outcome Measures
Exhaled Breath Condensate pH
CFQ-R
Serum Sildenafil Levels
Full Information
NCT ID
NCT00659529
First Posted
April 14, 2008
Last Updated
October 13, 2020
Sponsor
National Jewish Health
Collaborators
Cystic Fibrosis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00659529
Brief Title
Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease
Official Title
The Role of Phosphodiesterase Inhibitors in CF Lung Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
August 2008 (Actual)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Jewish Health
Collaborators
Cystic Fibrosis Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
cystic fibrosis, inflammation, pH, EBC, sputum biomarkers, phosphodiesterase inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
sildenafil
Other Intervention Name(s)
Revatio
Intervention Description
Sildenafil will be given 20mg po tid for 1 week, and then will be give 40mg po tid for 5 weeks.
Primary Outcome Measure Information:
Title
Sputum Elastase
Time Frame
Pre/post therapy
Secondary Outcome Measure Information:
Title
Exhaled Breath Condensate pH
Time Frame
Pre/post therapy
Title
CFQ-R
Time Frame
Pre/post therapy
Title
Serum Sildenafil Levels
Time Frame
Pre/during therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer L Taylor-Cousar, MD
Organizational Affiliation
National Jewish Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
17586695
Citation
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.
Results Reference
background
PubMed Identifier
25466700
Citation
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.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease
We'll reach out to this number within 24 hrs