Cystic FibrosisPhase 2CF-FLOWNCT02057458
Blood Flow and Vascular Function in Cystic Fibrosis
A Phase 2 study testing Sildenafil (Acute-1 hour) and Sildenafil (Subchronic-4 weeks) in people with Cystic Fibrosis, run by Augusta University at 1 site in United States.
Trial summary
Cystic fibrosis (CF) has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Sildenafil (Acute-1 hour) and Sildenafil (Subchronic-4 weeks)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Jul 2018
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of CF and healthy controls
- Men and women (greater than 18 yrs. old)
- Resting oxygen saturation (room air) greater than 90%
- Forced expiratory volume (FEV1) percent predicted greater than 30%
- Patients with or without CF related diabetes
- Traditional CF-treatment medications
- Ability to perform reliable/reproducible pulmonary function tests (PFT)
- Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)
Who cannot join
- Children less than 17 years old
- Body mass less than 20 kg
- A diagnosis of pulmonary arterial hypertension (PAH)
- FEV1 less than 30% of predicted
- Resting oxygen saturation (SpO2) less than 90%
- Self-reported to be a smoker
Show all 10Show fewer
- Current use of any vaso-active medications
- History of migraine headaches
- Pregnant or nursing at the time of the investigation
- A clinical diagnosis of cardiovascular disease, hypertension, or CF related diabetes
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis
Cystic fibrosis (CF) has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. The investigators laboratory recently published the first evidence of systemic vascular dysfunction in patients with CF. Therefore, it is reasonable to suspect that the blood vessels are involved with exercise intolerance in CF. This study will look at how 1) blood flow and 2) artery function contribute to exercise capacity in CF.
Read the detailed description
The most disturbing aspect of Cystic Fibrosis (CF) is the associated premature death. Low exercise capacity predicts death in patients with CF and is also associated with a steeper decline in lung function and more lung infections. A critical barrier to improving exercise tolerance in patients with CF is the investigators lack of knowledge regarding the different physiological mechanisms which contribute to their lower exercise capacity. We have compelling data to indicate that the blood vessels may contribute to the low exercise capacity in CF. The impact of this proof of concept investigation will test Phosphodiesterase Type 5 inhibitors (PDE5) inhibitors as a potential therapy in CF and will explore blood flow and endothelial function as potential mechanisms which contribute to exercise intolerance in CF. Improvements in exercise capacity will not only contribute to a better quality of live for patients with CF, it will also increase longevity in these patients.
- Conditions
- Cystic Fibrosis
- Being tested
- Sildenafil (Acute-1 hour), Sildenafil (Subchronic-4 weeks), Placebo
- Keywords
- arterial stiffness, flow-mediated dilation, endothelial function, pulse wave velocity, inflammation, oxidative stress, pulmonary function test, Cystic Fibrosis, Lung Disease, Nitric Oxide, Exercise Capacity, CF, Muscle Function, Sildenafil, Viagra, Revatio
- Medical subject headings
- Cystic Fibrosis, Inflammation, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil (Acute-1 hour)Drug
Also called Viagra, Revatio
Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg)
Sildenafil (Subchronic-4 weeks)Drug
Also called Viagra, Revatio
Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks
PlaceboDrug
Sugar pill designed to mimic the sildenafil treatment
| Study group | Role | What they receive |
|---|---|---|
| Acute Study: Sildenafil first, then Placebo | Experimental | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. Receives: Drug: Sildenafil (Acute-1 hour); Drug: Placebo |
| Acute Study: Placebo first, then Sildenafil | Experimental | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. Receives: Drug: Sildenafil (Acute-1 hour); Drug: Placebo |
| Sub-Chronic Study Sildenafil | Experimental | Following the acute study, patients will be instructed to take 20 mg of sildenafil, three times a day, for 4 weeks. Endothelial function will be determined within 48 hours following the last dose. Receives: Drug: Sildenafil (Subchronic-4 weeks) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Study: Percentage Flow-Mediated Dilation (FMD)
FMD determined one hour after ingestion of 50 mg Sildenafil or placebo
Measured: pre-treatment Baseline and 1 hour post-treatment
Baseline Diameter
Brachial Artery Diameter during FMD (pre-occlusion or "baseline")
Measured: pre-treatment Baseline and following 4 weeks sub-chronic treatment
Peak Diameter
Peak Brachial Artery Diameter during FMD (post-occlusion)
Measured: pre-treatment Baseline and following 4 weeks sub-chronic treatment
Absolute Change in Diameter
Absolute change in brachial artery diameter taken from the FMD assessment
Measured: pre-treatment Baseline and following 4 weeks sub-chronic treatment
FEV1 (% Predicted)
Forced Expiratory Volume in the first second expressed as a percent predicted.
Measured: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
VO2 Peak (Absolute)
absolute (L/min) peak oxygen consumption during maximal exercise test
Measured: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
VO2 Peak (Relative)
relative (mL/kg/min) peak oxygen consumption during maximal exercise test
Measured: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
VO2 Peak (Percent Predicted)
Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test.
Measured: pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment
VE Peak
peak ventilation (L/min) during maximal exercise test
Measured: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
RER Peak
peak respiratory exchange ratio during maximal exercise test
Measured: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionJul 2018
- Study completionJul 2018
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 (1)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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ryan Harris, Augusta University
- Investigators
- Ryan Harris, Ph.D., Principal investigator, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02057458
- Sponsor's protocol ID
- DK100783
- Other IDs
- R21DK100783
- Acronym
- CF-FLOW
- Status last verified
- Apr 2020
- First submitted
- 4 Feb 2014
- Last updated
- 24 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Rodriguez-Miguelez P, Seigler N, Ishii H, Crandall R, McKie KT, Forseen C, Harris RA. Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle. Med Sci Sports Exerc. 2021 Apr 1;53(4):684-693. doi: 10.1249/MSS.0000000000002521.
PubMed 33105385
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT02057458
- Acronym / sponsor ID
- CF-FLOW / DK100783
- Conditions
- Cystic Fibrosis
- Keywords
- arterial stiffness, flow-mediated dilation, endothelial function, pulse wave velocity, inflammation, oxidative stress, pulmonary function test, Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Apr 2014 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 7 Feb 2014 (estimated)
- Results
- Posted 24 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystic fibrosis (CF) has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. The investigators laboratory recently published the first evidence of systemic vascular dysfunction in patients with CF. Therefore, it is reasonable to suspect that the blood vessels are involved with exercise intolerance in CF. This study will look at how 1) blood flow and 2) artery function contribute to exercise capacity in CF.
Detailed description
The most disturbing aspect of Cystic Fibrosis (CF) is the associated premature death. Low exercise capacity predicts death in patients with CF and is also associated with a steeper decline in lung function and more lung infections. A critical barrier to improving exercise tolerance in patients with CF is the investigators lack of knowledge regarding the different physiological mechanisms which contribute to their lower exercise capacity. We have compelling data to indicate that the blood vessels may contribute to the low exercise capacity in CF. The impact of this proof of concept investigation will test Phosphodiesterase Type 5 inhibitors (PDE5) inhibitors as a potential therapy in CF and will explore blood flow and endothelial function as potential mechanisms which contribute to exercise intolerance in CF. Improvements in exercise capacity will not only contribute to a better quality of live for patients with CF, it will also increase longevity in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Acute Study: Sildenafil first, then Placebo | Experimental | Drug: Sildenafil (Acute-1 hour), Drug: PlaceboIn randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
| Acute Study: Placebo first, then Sildenafil | Experimental | Drug: Sildenafil (Acute-1 hour), Drug: PlaceboIn randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
| Sub-Chronic Study Sildenafil | Experimental | Drug: Sildenafil (Subchronic-4 weeks)Following the acute study, patients will be instructed to take 20 mg of sildenafil, three times a day, for 4 weeks. Endothelial function will be determined within 48 hours following the last dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of CF and healthy controls
- Men and women (greater than 18 yrs. old)
- Resting oxygen saturation (room air) greater than 90%
- Forced expiratory volume (FEV1) percent predicted greater than 30%
- Patients with or without CF related diabetes
Key exclusion criteria (10 listed)
- Children less than 17 years old
- Body mass less than 20 kg
- A diagnosis of pulmonary arterial hypertension (PAH)
- FEV1 less than 30% of predicted
- Resting oxygen saturation (SpO2) less than 90%
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 (Acute-1 hour)Also: Viagra, RevatioVascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg) | Drug | Acute Study: Placebo first, then Sildenafil, Acute Study: Sildenafil first, then Placebo |
| Sildenafil (Subchronic-4 weeks)Also: Viagra, RevatioVascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks | Drug | Sub-Chronic Study Sildenafil |
| PlaceboSugar pill designed to mimic the sildenafil treatment | Drug | Acute Study: Placebo first, then Sildenafil, Acute Study: Sildenafil first, then Placebo |
Primary outcome
Acute Study: Percentage Flow-Mediated Dilation (FMD)
Time frame: pre-treatment Baseline and 1 hour post-treatment
FMD determined one hour after ingestion of 50 mg Sildenafil or placebo
Baseline Diameter
Time frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
Brachial Artery Diameter during FMD (pre-occlusion or "baseline")
Peak Diameter
Time frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
Peak Brachial Artery Diameter during FMD (post-occlusion)
Absolute Change in Diameter
Time frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
Absolute change in brachial artery diameter taken from the FMD assessment
FEV1 (% Predicted)
Time frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Forced Expiratory Volume in the first second expressed as a percent predicted.
VO2 Peak (Absolute)
Time frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
absolute (L/min) peak oxygen consumption during maximal exercise test
VO2 Peak (Relative)
Time frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
relative (mL/kg/min) peak oxygen consumption during maximal exercise test
VO2 Peak (Percent Predicted)
Time frame: pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment
Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test.
VE Peak
Time frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
peak ventilation (L/min) during maximal exercise test
RER Peak
Time frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
peak respiratory exchange ratio during maximal exercise test
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33105385Rodriguez-Miguelez P, Seigler N, Ishii H, Crandall R, McKie KT, Forseen C, Harris RA. Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle. Med Sci Sports Exerc. 2021 Apr 1;53(4):684-693. doi: 10.1249/MSS.0000000000002521.
- Laboratory of Integrative Vascular and Exercise PhysiologyLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Ryan Harris, Ph.D. principal investigator
Augusta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil (Acute-1 hour) and Sildenafil (Subchronic-4 weeks) in people with Cystic Fibrosis, run by Augusta University at 1 site 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 10 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 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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 24 Apr 2020). 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?
Acute Study: Percentage Flow-Mediated Dilation (FMD) (time frame: pre-treatment Baseline and 1 hour post-treatment). The study lists 10 primary outcomes in all. 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 NCT02057458, which also lists 1 linked publication.
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 24 Apr 2020.