Cystic FibrosisPhase 2/3NCT04039087
Sildenafil Exercise: Role of PDE5 Inhibition
A Phase 2/3 study testing Sildenafil 40mg oral capsule in people with Cystic Fibrosis, run by National Jewish Health at 2 sites in United States.
Trial summary
Exercise intolerance is an understudied phenomenon in people with CF. The investigators hypothesized that vascular dysfunction plays a significant role, and can be partially reversed by administration of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil. Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Sildenafil 40mg oral capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Sep 2019to 30 Jun 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of cystic fibrosis (CF) based on the following criteria: Positive sweat chloride concentration ≥60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or genotype with two identifiable disease-causing mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
- Male or female patients ≥ 9 years of age
- forced expiratory volume at one second (FEV1) ≥ 30% predicted and ≤ 80% for patients ≥ 18 years of age and ≤ 85% for patients < 18 years of age
- 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
- Resting oxygen saturation (room air) ≥ 85%
- Patients with or without CF related diabetes
- Ability to perform spirometry reproducibly (according to American Thoracic Society) criteria
- Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)
Who cannot join
- Children 8 yrs. old and younger
- Subjects who weigh < 20 Kgs
- 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 for women of child-bearing potential.
- History of significant hepatic disease (aspartate transaminase or alanine transaminase > 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
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- History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
- History of severe neurological disease (e.g. history of stroke),
- History of severe hematologic disease (e.g. history of bleeding diathesis; current international normalized ratio (INR) > 2.0
- History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
- History of severe renal impairment (creatinine >1.8 mg/dL.)
- Inability to swallow pills
- Previous organ transplantation
- Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
- Use of concomitant medications known to be potent inhibitors of CYP3A4 [e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin (currently or within one month of initiation of study drug)] (NOTE: use of azithromycin is NOT a cause for exclusion)
- History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacteria massiliense within 2 years of screening
- History of migraine headaches.
- 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
- Initiation of a cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy less than 1 month prior to first dose of sildenafil or placebo
- Use of anticoagulants
- Frank pulmonary hypertension[right ventricular systolic pressure (RVSP) >40 mm Hg by echocardiography)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Augusta University
Augusta, Georgia, 30912
National Jewish Health
Denver, Colorado, 80206
About this study
Official title: Mechanisms of Exercise Intolerance in Cystic Fibrosis: Role of PDE5 Inhibition
Exercise intolerance is an understudied phenomenon in people with CF. The investigators hypothesized that vascular dysfunction plays a significant role, and can be partially reversed by administration of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil.
Read the detailed description
While cystic fibrosis (CF) is most common in people of European ancestry, it can occur in individuals of any ethnicity. The predicted median life expectancy age for patients with CF is 47.7 years compared to 78.8 years in the general U.S. population. Exercise intolerance, evaluated as a reduction in exercise capacity (VO2 peak), has been shown to predict mortality in patients with CF independent of lung function. A critical barrier to improving exercise tolerance in CF is the lack of knowledge regarding the different physiological mechanisms which contribute to decreased exercise capacity. The present investigation will not only evaluate the impact that sildenafil has on clinically relevant and patient oriented outcomes, it will also provide mechanistic insight.
Phosphodiesterase type 5 (PDE5) inhibitors reduce inflammation, improve vascular health, increase microvascular O2 delivery and improve skeletal muscle function. Accordingly, the central hypothesis of the study is that treatment with the PDE5 inhibitor, sildenafil, can improve exercise capacity, vascular and cardiac function, and overall quality of life, all of which may contribute to improvement in exercise tolerance in people with CF
- Conditions
- Cystic Fibrosis
- Being tested
- Sildenafil 40mg oral capsule, Placebo Oral capsule
- Keywords
- Exercise intolerance, Quality of life, Cardiac function
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil 40mg oral capsuleDrug
Also called sildenafil, revatio
40 mg, sildenafil capsule taken by mouth thrice daily
Placebo Oral capsuleDrug
Also called placebo
Placebo capsule taken by mouth thrice daily
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Active comparator | active sildenafil 40 mg p.o. three times per day Receives: Drug: Sildenafil 40mg oral capsule |
| Placebo Arm | Placebo comparator | placebo three times per day Receives: Drug: Placebo Oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Minute Walk Distance (6MWD)
Exercise capacity, an objective measurement of exercise tolerance, predicts mortality in patients with CF. The mechanisms for exercise intolerance in CF have yet to be fully elucidated and further understanding could improve clinical outcomes and survival in CF. Preliminary data from two independent proof-of-concept clinical trials support the use of sildenafil to improve exercise capacity, cardiac function, and quality of life in CF
Measured: Change in distance walked between week 1 and week 13
Secondary outcomes (1)
Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The respiratory domain of the validated CF-specific quality of life measure. The CFQ-R Respiratory domain score (scale 0-100 with higher scores indicating better quality of life).
Measured: Quality of life assessed at weeks 1 and 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start5 Sep 2019
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized 1:1 to the sildenafil or placebo groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Collaborators
- Augusta University, Cystic Fibrosis Foundation
- Responsible party
- Principal investigator, Jennifer Taylor-Cousar, National Jewish Health
- Investigators
- Jennifer Taylor-Cousar, MD, MSCS, Principal investigator, National Jewish Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04039087
- Sponsor's protocol ID
- Sildenafil Exercise
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2019
- Last updated
- 28 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25466700Rodriguez-Miguelez P, Lee N, Tucker MA, Csanyi G, McKie KT, Forseen C, Harris RA. Sildenafil improves vascular endothelial function in patients with cystic fibrosis. Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1486-H1494. doi: 10.1152/ajpheart.00301.2018. Epub 2018 Aug 31.
PubMed 30168731
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Exercise Intolerance in Cystic Fibrosis: Role of PDE5 Inhibition
- ClinicalTrials.gov ID
- NCT04039087
- Acronym / sponsor ID
- Sildenafil Exercise
- Conditions
- Cystic Fibrosis
- Keywords
- Exercise intolerance, Quality of life, Cardiac function
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Jewish HealthUniversity, hospital or other
- Collaborators
- Augusta University, Cystic Fibrosis Foundation
- Study start
- 5 Sep 2019 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 31 Jul 2019 (actual)
- Results
- Posted 28 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Exercise intolerance is an understudied phenomenon in people with CF. The investigators hypothesized that vascular dysfunction plays a significant role, and can be partially reversed by administration of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil.
Detailed description
While cystic fibrosis (CF) is most common in people of European ancestry, it can occur in individuals of any ethnicity. The predicted median life expectancy age for patients with CF is 47.7 years compared to 78.8 years in the general U.S. population. Exercise intolerance, evaluated as a reduction in exercise capacity (VO2 peak), has been shown to predict mortality in patients with CF independent of lung function. A critical barrier to improving exercise tolerance in CF is the lack of knowledge regarding the different physiological mechanisms which contribute to decreased exercise capacity. The present investigation will not only evaluate the impact that sildenafil has on clinically relevant and patient oriented outcomes, it will also provide mechanistic insight.
Phosphodiesterase type 5 (PDE5) inhibitors reduce inflammation, improve vascular health, increase microvascular O2 delivery and improve skeletal muscle function. Accordingly, the central hypothesis of the study is that treatment with the PDE5 inhibitor, sildenafil, can improve exercise capacity, vascular and cardiac function, and overall quality of life, all of which may contribute to improvement in exercise tolerance in people with CF
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized 1:1 to the sildenafil or placebo groups
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Active comparator | Drug: Sildenafil 40mg oral capsuleactive sildenafil 40 mg p.o. three times per day |
| Placebo Arm | Placebo comparator | Drug: Placebo Oral capsuleplacebo three times per day |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of cystic fibrosis (CF) based on the following criteria: Positive sweat chloride concentration ≥60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or genotype with two identifiable disease-causing mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
- Male or female patients ≥ 9 years of age
- forced expiratory volume at one second (FEV1) ≥ 30% predicted and ≤ 80% for patients ≥ 18 years of age and ≤ 85% for patients < 18 years of age
- 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
- Resting oxygen saturation (room air) ≥ 85%
Key exclusion criteria (21 listed)
- Children 8 yrs. old and younger
- Subjects who weigh < 20 Kgs
- 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 for women of child-bearing potential.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil 40mg oral capsuleAlso: sildenafil, revatio40 mg, sildenafil capsule taken by mouth thrice daily | Drug | Sildenafil |
| Placebo Oral capsuleAlso: placeboPlacebo capsule taken by mouth thrice daily | Drug | Placebo Arm |
Primary outcome
6 Minute Walk Distance (6MWD)
Time frame: Change in distance walked between week 1 and week 13
Exercise capacity, an objective measurement of exercise tolerance, predicts mortality in patients with CF. The mechanisms for exercise intolerance in CF have yet to be fully elucidated and further understanding could improve clinical outcomes and survival in CF. Preliminary data from two independent proof-of-concept clinical trials support the use of sildenafil to improve exercise capacity, cardiac function, and quality of life in CF
1 secondary outcome
Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: Quality of life assessed at weeks 1 and 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25466700Taylor-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.
- Background: PubMed 30168731Rodriguez-Miguelez P, Lee N, Tucker MA, Csanyi G, McKie KT, Forseen C, Harris RA. Sildenafil improves vascular endothelial function in patients with cystic fibrosis. Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1486-H1494. doi: 10.1152/ajpheart.00301.2018. Epub 2018 Aug 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Taylor-Cousar, MD, MSCS principal investigator
National Jewish Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sildenafil 40mg oral capsule in people with Cystic Fibrosis, run by National Jewish Health at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 Minute Walk Distance (6MWD) (time frame: Change in distance walked between week 1 and week 13). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04039087, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.