Cystic FibrosisCFNCT04549077
Pulmonary Vascular Disease in CF
An observational study of Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
Trial summary
In this project, the investigators seek to understand the role of endothelial cells in Cystic Fibrosis (CF) lung disease. This objective will be achieved by conducting a cross sectional clinical study to define the morphology of the pulmonary circulation across a range of lung function coupled with a mechanistic study… Read more about this study
- Who is it for?
- Ages 5 to 21 years
- Conditions the study is for
- Cystic Fibrosis
- How many people
- 86 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Jul 2020to 1 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 5 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: 93 subjects with cystic fibrosis, 5-21 years of age, equally divided between males and females will be recruited from 2 CF centers; Cincinnati Children's Hospital and Riley Children's Hospital.
Who may be able to join
- 5-21 years of age
- diagnosis of CF based on a positive sweat test and genetic testing
- Baseline pulmonary condition defined as a) Absence of signs and symptoms of pulmonary exacerbation, b) Baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months, c) Patients should be off acute antibiotics for 2 weeks or longer.
- Subjects should be able to perform an acceptable and reproducible spirometry
- Study population will be equally divided between three groups based on FEV1%, (FEV1% ≥ 90); moderate (60 ≤ FEV1% < 90)
- solid tumor diagnosis
- had chest CT scan to survey possible metastasis or any other lung disease
- age and gender matched to Cystic Fibrosis patients
Who cannot join
- Enrollment in clinical trials of CFTR correctors and or potentiator
- Enrollment in gene therapy trial
- Pregnancy.
- Historical Controls
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3026
Riley Hospital for Children
Indianapolis, Indiana, 46204-3509
About this study
Official title: Pulmonary Vascular Disease in Cystic Fibrosis
In this project, the investigators seek to understand the role of endothelial cells in Cystic Fibrosis (CF) lung disease. This objective will be achieved by conducting a cross sectional clinical study to define the morphology of the pulmonary circulation across a range of lung function coupled with a mechanistic study of the effect of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in endothelial cells on vasculogenesis, epithelial morphogenesis and epithelial CFTR function. Toward that end, the investigators propose the following hypotheses; (a). Loss of pulmonary small blood vessels begins early in the CF lung and worsens with disease progression, (b).VEGFR2-CFTR interactions happen at the plasma membrane of endothelial cells and is likely to be involved in transendothelial ion transport (c) impaired VEGFR2-CFTR interactions on the endothelial cells will have a profound effect on vasculogenesis, epithelial morphogenesis and ion transport.
The first hypotheses will be tested through this clinical study. The following 2 hypotheses will be tested through laboratory studies that do not involve human subjects.
Read the detailed description
Pulmonary disease in Cystic Fibrosis (CF) is characterized by progressive loss of functional gas exchange units that eventually results in respiratory failure. In CF lung disease, remodeling of pulmonary blood vessels, and vascular growth of bronchial blood vessels leading to systemic vascularization of the lung are the principal characteristics of pulmonary vascular disease. Studies have demonstrated that abnormal perfusion is present in up to 85% of 1 year old CF infants and only 17% of the perfusion deficits could be explained by mucus plugging or bronchial wall abnormalities at this age. Based on the investigators' state of the art method to reconstruct the pulmonary vasculature from non-contrast high resolution CT scan of the lungs, the investigators demonstrated that the blood volume in small vessels begins to decline when lung function is still in the normal range and worsens with increase disease severity. Furthermore, the investigators have also demonstrated that systemic vascularization of the lungs by the bronchial circulation begins at a FEV1% of 100. Preclinical studies of pulmonary endothelium revealed that delivering vascular endothelial growth factor receptor (VEGFR) antagonist to rats leads to air space enlargement and pruning of the pulmonary arterial tree. Thus, there is a central unanswered question as to whether pulmonary vascular disease (vascular remodeling and systemic vascularization) are just a squeal of parenchymal destruction or whether they contribute to the loss of alveolar gas exchange units and decline in lung function. In this proposal, the investigators will accomplish the following aims: 1) describe the morphology of the pulmonary vasculature across a wide range of lung function and relate the findings to functional outcomes, 2) examine mechanism of early loss of small blood vessels in CF patients as it relates to endothelial CFTR dysfunction. In addition, the investigators will study the changes in the pulmonary circulation after the initiation of triple combination therapy Trikafta (elexacaftor, ivacaftor, and tezacaftor).
This is a case control study of 93 cystic fibrosis patients and 100 age and gender matched controls. CF patients (cases) will be recruited from two cystic fibrosis centers, Cincinnati Children's Hospital and Riley Children's Hospital. Controls will be subjects from the oncology service without lung disease who had CT scan of the chest to rule out pulmonary metastasis. 31 subjects of the 93 subjects enrolled will receive a second evaluation 6 months after starting a clinically prescribed corrector / modulator of Cystic Fibrosis Transmembrane Conductance Protein Regulator (Trikafta) that was approved by the FDA in October, 2019 for patients with CF ages 12 and up. If FDA approval for use of Trikafta for ages 6-11 years of age is obtained, this patient age range will also be eligible for the second evaluation at 6 months.
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Pulmonary Disease, Pediatric
- Medical subject headings
- Cystic Fibrosis, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cystic Fibrosis Patients | Patients with Cystic Fibrosis. | |
| Historical Controls | Patients diagnosed with solid tumors, who have had a normal chest CT scan during screening for possible metastasis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
In Aim 1A, the reconstruction of pulmonary vasculature will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
Measured: At baseline
The change in the the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
In Aim 1A, the change in the reconstruction of pulmonary vasculature between the baseline and 6 month visit imaging will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
Measured: For a subset of 31 patients, the change in ratio will be measured between the baseline visit and 6 months post Trikafta therapy.
Secondary outcomes (2)
Forced Expiratory Volume as a percent of the referenced value (FEV1%)
Forced Expiratory Volume as a percent of the referenced value (FEV1%)
Measured: Baseline
The change in Forced Expiratory Volume as a percent of the referenced value (FEV1%)
The change in Forced Expiratory Volume as a percent of the referenced value (FEV1%)
Measured: For a subset of 31 patients, the change from baseline to 6 months post Trikafta therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start29 Jul 2020
- Primary completion14 Nov 2024
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549077
- Sponsor's protocol ID
- 2019-1239
- Acronym
- CF
- Status last verified
- Jan 2026
- First submitted
- 9 Aug 2020
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Vascular Disease in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT04549077
- Acronym / sponsor ID
- CF / 2019-1239
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Pulmonary Disease, Pediatric
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- 14 Nov 2024 (actual)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this project, the investigators seek to understand the role of endothelial cells in Cystic Fibrosis (CF) lung disease. This objective will be achieved by conducting a cross sectional clinical study to define the morphology of the pulmonary circulation across a range of lung function coupled with a mechanistic study of the effect of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in endothelial cells on vasculogenesis, epithelial morphogenesis and epithelial CFTR function. Toward that end, the investigators propose the following hypotheses; (a). Loss of pulmonary small blood vessels begins early in the CF lung and worsens with disease progression, (b).VEGFR2-CFTR interactions happen at the plasma membrane of endothelial cells and is likely to be involved in transendothelial ion transport (c) impaired VEGFR2-CFTR interactions on the endothelial cells will have a profound effect on vasculogenesis, epithelial morphogenesis and ion transport.
The first hypotheses will be tested through this clinical study. The following 2 hypotheses will be tested through laboratory studies that do not involve human subjects.
Detailed description
Pulmonary disease in Cystic Fibrosis (CF) is characterized by progressive loss of functional gas exchange units that eventually results in respiratory failure. In CF lung disease, remodeling of pulmonary blood vessels, and vascular growth of bronchial blood vessels leading to systemic vascularization of the lung are the principal characteristics of pulmonary vascular disease. Studies have demonstrated that abnormal perfusion is present in up to 85% of 1 year old CF infants and only 17% of the perfusion deficits could be explained by mucus plugging or bronchial wall abnormalities at this age. Based on the investigators' state of the art method to reconstruct the pulmonary vasculature from non-contrast high resolution CT scan of the lungs, the investigators demonstrated that the blood volume in small vessels begins to decline when lung function is still in the normal range and worsens with increase disease severity. Furthermore, the investigators have also demonstrated that systemic vascularization of the lungs by the bronchial circulation begins at a FEV1% of 100. Preclinical studies of pulmonary endothelium revealed that delivering vascular endothelial growth factor receptor (VEGFR) antagonist to rats leads to air space enlargement and pruning of the pulmonary arterial tree. Thus, there is a central unanswered question as to whether pulmonary vascular disease (vascular remodeling and systemic vascularization) are just a squeal of parenchymal destruction or whether they contribute to the loss of alveolar gas exchange units and decline in lung function. In this proposal, the investigators will accomplish the following aims: 1) describe the morphology of the pulmonary vasculature across a wide range of lung function and relate the findings to functional outcomes, 2) examine mechanism of early loss of small blood vessels in CF patients as it relates to endothelial CFTR dysfunction. In addition, the investigators will study the changes in the pulmonary circulation after the initiation of triple combination therapy Trikafta (elexacaftor, ivacaftor, and tezacaftor).
This is a case control study of 93 cystic fibrosis patients and 100 age and gender matched controls. CF patients (cases) will be recruited from two cystic fibrosis centers, Cincinnati Children's Hospital and Riley Children's Hospital. Controls will be subjects from the oncology service without lung disease who had CT scan of the chest to rule out pulmonary metastasis. 31 subjects of the 93 subjects enrolled will receive a second evaluation 6 months after starting a clinically prescribed corrector / modulator of Cystic Fibrosis Transmembrane Conductance Protein Regulator (Trikafta) that was approved by the FDA in October, 2019 for patients with CF ages 12 and up. If FDA approval for use of Trikafta for ages 6-11 years of age is obtained, this patient age range will also be eligible for the second evaluation at 6 months.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cystic Fibrosis Patients | – | –Patients with Cystic Fibrosis. |
| Historical Controls | – | –Patients diagnosed with solid tumors, who have had a normal chest CT scan during screening for possible metastasis |
Who may qualify
- Ages
- 5 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- 93 subjects with cystic fibrosis, 5-21 years of age, equally divided between males and females will be recruited from 2 CF centers; Cincinnati Children's Hospital and Riley Children's Hospital.
Key inclusion criteria (8 listed)
- 5-21 years of age
- diagnosis of CF based on a positive sweat test and genetic testing
- Baseline pulmonary condition defined as a) Absence of signs and symptoms of pulmonary exacerbation, b) Baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months, c) Patients should be off acute antibiotics for 2 weeks or longer.
- Subjects should be able to perform an acceptable and reproducible spirometry
- Study population will be equally divided between three groups based on FEV1%, (FEV1% ≥ 90); moderate (60 ≤ FEV1% < 90)
Key exclusion criteria (4 listed)
- Enrollment in clinical trials of CFTR correctors and or potentiator
- Enrollment in gene therapy trial
- Pregnancy.
- Historical Controls
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
Time frame: At baseline
In Aim 1A, the reconstruction of pulmonary vasculature will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
The change in the the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
Time frame: For a subset of 31 patients, the change in ratio will be measured between the baseline visit and 6 months post Trikafta therapy.
In Aim 1A, the change in the reconstruction of pulmonary vasculature between the baseline and 6 month visit imaging will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).
2 secondary outcomes
Forced Expiratory Volume as a percent of the referenced value (FEV1%)
Time frame: Baseline
The change in Forced Expiratory Volume as a percent of the referenced value (FEV1%)
Time frame: For a subset of 31 patients, the change from baseline to 6 months post Trikafta therapy.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati 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 4 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: under way, not looking for participants, as of the sponsor's last update on 14 Sep 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV). (time frame: At baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2026.