Cystic FibrosisPhase 4NCT04467957
Non-contrast Lung Perfusion Mapping Applied for New Insights in Cystic Fibrosis
A Phase 4 study testing Initiation of CFTR Modulator and Hyperpolarized Xenon 129 in people with Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
Cystic fibrosis (CF) results in the thickening of mucus in the lungs and other organs due to dysfunction of a transmembrane conductance protein. This allows buildup of bacteria that results in inflammation, leading to tissue breakdown and loss of function. Read more about this study
- Who is it for?
- Ages 6 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Initiation of CFTR Modulator and Hyperpolarized Xenon 129
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2020to 31 Dec 2026
- Phase
- Phase 4
- 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 6 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- male or female between the ages of 6 through 21 years
- diagnosis of CF by positive sweat test and genetic test
- planning to start Trikafta based on clinical decision
- baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months
- Absence of exacerbation defined as
- No acute antibiotic usage for 14 days prior to MRI visit
Show all 10Show fewer
- Able to perform an acceptable and reproducible spirometry
- O2 saturation level at 90% or greater when laying flat
- male or female between the ages of 6 through 21 years
- no known diagnoses that impact lung function in the opinion of the investigators
Who cannot join
- standard MRI exclusions (metal implants, claustrophobia)
- pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Cystic fibrosis (CF) results in the thickening of mucus in the lungs and other organs due to dysfunction of a transmembrane conductance protein. This allows buildup of bacteria that results in inflammation, leading to tissue breakdown and loss of function. In the lungs, this process causes loss of air exchange structures progressing to diminished lung function. The exchange of oxygen in the lungs depends on both the integrity of air conduits and vasculature. Most clinical assessments, however, focus on ventilatory function, with the assumption that any vascular compromise is secondary. Nevertheless, there is evidence, some from the investigator's lab, to suggest that perfusion anomalies in the lung occur before signs of ventilatory dysfunction. Thus, the inflammatory processes of CF may impact pulmonary microvasculature specifically and concurrently or prior to damage to ventilatory structures. This study aims to apply a new MRI method to serially measure regional lung perfusion, without the use of contrast agent, in children with CF and to associate it with regional assessments of ventilation and to serum cytokines or proteomic markers of angiogenesis and inflammatory processes.
The investigator's lab has recently developed a noninvasive, non-contrast, method of labeling blood flowing into the lungs and generating a map of perfusion. The investigator aims to couple this technique to existing methods using hyperpolarized Xenon to map ventilation. The investigator will apply these methods over time in CF patients, monitoring the relationship between regional perfusion and ventilation defects.
This pilot work will provide the foundation for larger studies to establish the essential etiological role of perfusion deficits in CF.
Read the detailed description
The Lung Perfusion in CF trial is a case-control observational study conducted at Cincinnati Children's Hospital.
Patients will be assessed before and approximately 6 months after the clinical initiation of triple-combination modulator therapy with the following imaging to demonstrate aim 1, that pulmonary perfusion is regionally altered in CF patients in association with the status and progression of lung ventilatory function: Ultra-short echo time (UTE) protocol to obtain structural lung imaging primarily for anatomic reference, Hyperpolarized Xenon gas inhalation protocol to measure regional lung ventilation and arterial spin labeling protocol to measure regional lung perfusion.
To demonstrate aim 2, that different profiles of serum proteomic markers related to angiogenesis and vascular remodeling, characterize states of pulmonary hyperfusion and hypoperfusion, blood sample data analysis from a separate study conducted at Cincinnati Children's Hospital Medical Center will also be obtained before and 6 months after initiation of triple-combination modulator therapy.
Safety will be assessed by recording adverse events. Vital signs (heart rate, SPO2) will be recorded before, immediately following inhalation, and 2 minutes after each Xenon gas inhalation; O2 saturation will be monitored continuously throughout the Xenon portion of the MRI, and the time and duration of nadir will be recorded.
The overarching goal of this study is to demonstrate that arterial spin labeling MRI lung perfusion can be used to measure regional manifestations of pulmonary vascular disease in CF that precedes and contributes to global and local decline in ventilatory lung function.
- Conditions
- Cystic Fibrosis
- Being tested
- Initiation of CFTR Modulator, Hyperpolarized Xenon 129
- Keywords
- Cystic Fibrosis, Cystic fibrosis transmembrane conductance regulator modulator therapy, hyperpolarized xenon, Cystic fibrosis transmembrane conductance regulator (CFTR)
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Initiation of CFTR ModulatorDrug
Also called 129Xe
Inhaled contrast for MRI occurring at each visit
Hyperpolarized Xenon 129Drug
Also called 129Xe
Inhaled contrast for MRI occurring at each visit
| Study group | Role | What they receive |
|---|---|---|
| CF Cohort | Experimental | 16 Cystic Fibrosis Patients will undergo MRI imaging before and 6 months after initiation of triple-combination modulator therapy. Initiation of triple -combination modulator therapy will be determined by clinician and family prior to study enrollment. Hyperpolarized Xenon 129 will be administered through inhalation at two MRI imaging study visits. Receives: Drug: Initiation of CFTR Modulator; Drug: Hyperpolarized Xenon 129 |
| Control Cohort | Experimental | 10 Healthy control study participants matched for age and gender will undergo one MRI imaging study visit. Hyperpolarized Xenon 129 will be administered through inhalation at one MRI imaging study visit. Receives: Drug: Hyperpolarized Xenon 129 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilation Defect Percentage (VDP)
Lung defect calculations (total and lobar defect percentages) will be performed by evaluating the percentage of voxels with signals below a threshold value of 60% of the total lung mean signal. This threshold (60%) represents our estimate of the visually accurate defect selection threshold for CF patients. To assign the pixels in the hyperpolarized Xenon gas (129Xe) MRI slices to a lobe, corresponding CT and/or UTE MRI images will be segmented and analyzed with custom MATLAB software.
VDP for CF and Control groups will be compared by 2-sample T-test at baseline. VDP at baseline and 6 months for the CF group will be compared by paired T-test to determine if the change is significantly different from zero change.
Measured: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Perfusion Defect Percentage (PDP)
Similar to the VDP, total and lobar defect percentages will be calculated for lung perfusion.
As for VDP, PDP will be compared between CF and Control groups at baseline via 2-sample T-test.
PDP change from baseline to 6 months will be measured for the CF group via paired T-test to determine change significantly different from zero change.
Measured: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Degree of concordance between ventilation and perfusion defects
Degree of concordance between ventilation and perfusion defects will be calculated as percentage of overlap between ventilation and perfusion defect volumes.
Measured: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Proteome assays as global indicators of inflammatory/angiogenic processes
Proteome assays as global indicators of inflammatory/angiogenic processes, will be compared between groups by 2-sample T-test. Correlation analyses will be performed to examine associations between quantitative image scores for each modality (VDP and PDP) and lung function (FEV1%), as well as proteome concentrations.
Measured: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2020
- Study start15 Nov 2020
- Primary completion31 Dec 2025
- Study completion31 Dec 2026 (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.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark DiFrancesco, PhD, Principal investigator, CCHMCJason Woods, PhD, Study chair, CCHMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04467957
- Sponsor's protocol ID
- 2019-1192
- Status last verified
- Jan 2026
- First submitted
- 19 Jun 2020
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-contrast Lung Perfusion Mapping Applied for New Insights in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT04467957
- Acronym / sponsor ID
- 2019-1192
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Cystic fibrosis transmembrane conductance regulator modulator therapy, hyperpolarized xenon, Cystic fibrosis transmembrane conductance regulator (CFTR)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 15 Nov 2020 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 13 Jul 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.
Cystic fibrosis (CF) results in the thickening of mucus in the lungs and other organs due to dysfunction of a transmembrane conductance protein. This allows buildup of bacteria that results in inflammation, leading to tissue breakdown and loss of function. In the lungs, this process causes loss of air exchange structures progressing to diminished lung function. The exchange of oxygen in the lungs depends on both the integrity of air conduits and vasculature. Most clinical assessments, however, focus on ventilatory function, with the assumption that any vascular compromise is secondary. Nevertheless, there is evidence, some from the investigator's lab, to suggest that perfusion anomalies in the lung occur before signs of ventilatory dysfunction. Thus, the inflammatory processes of CF may impact pulmonary microvasculature specifically and concurrently or prior to damage to ventilatory structures. This study aims to apply a new MRI method to serially measure regional lung perfusion, without the use of contrast agent, in children with CF and to associate it with regional assessments of ventilation and to serum cytokines or proteomic markers of angiogenesis and inflammatory processes.
The investigator's lab has recently developed a noninvasive, non-contrast, method of labeling blood flowing into the lungs and generating a map of perfusion. The investigator aims to couple this technique to existing methods using hyperpolarized Xenon to map ventilation. The investigator will apply these methods over time in CF patients, monitoring the relationship between regional perfusion and ventilation defects.
This pilot work will provide the foundation for larger studies to establish the essential etiological role of perfusion deficits in CF.
Detailed description
The Lung Perfusion in CF trial is a case-control observational study conducted at Cincinnati Children's Hospital.
Patients will be assessed before and approximately 6 months after the clinical initiation of triple-combination modulator therapy with the following imaging to demonstrate aim 1, that pulmonary perfusion is regionally altered in CF patients in association with the status and progression of lung ventilatory function: Ultra-short echo time (UTE) protocol to obtain structural lung imaging primarily for anatomic reference, Hyperpolarized Xenon gas inhalation protocol to measure regional lung ventilation and arterial spin labeling protocol to measure regional lung perfusion.
To demonstrate aim 2, that different profiles of serum proteomic markers related to angiogenesis and vascular remodeling, characterize states of pulmonary hyperfusion and hypoperfusion, blood sample data analysis from a separate study conducted at Cincinnati Children's Hospital Medical Center will also be obtained before and 6 months after initiation of triple-combination modulator therapy.
Safety will be assessed by recording adverse events. Vital signs (heart rate, SPO2) will be recorded before, immediately following inhalation, and 2 minutes after each Xenon gas inhalation; O2 saturation will be monitored continuously throughout the Xenon portion of the MRI, and the time and duration of nadir will be recorded.
The overarching goal of this study is to demonstrate that arterial spin labeling MRI lung perfusion can be used to measure regional manifestations of pulmonary vascular disease in CF that precedes and contributes to global and local decline in ventilatory lung function.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CF Cohort | Experimental | Drug: Initiation of CFTR Modulator, Drug: Hyperpolarized Xenon 12916 Cystic Fibrosis Patients will undergo MRI imaging before and 6 months after initiation of triple-combination modulator therapy. Initiation of triple -combination modulator therapy will be determined by clinician and family prior to study enrollment. Hyperpolarized Xenon 129 will be administered through inhalation at two MRI imaging study visits. |
| Control Cohort | Experimental | Drug: Hyperpolarized Xenon 12910 Healthy control study participants matched for age and gender will undergo one MRI imaging study visit. Hyperpolarized Xenon 129 will be administered through inhalation at one MRI imaging study visit. |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- male or female between the ages of 6 through 21 years
- diagnosis of CF by positive sweat test and genetic test
- planning to start Trikafta based on clinical decision
- baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months
- Absence of exacerbation defined as
Key exclusion criteria (2 listed)
- standard MRI exclusions (metal implants, claustrophobia)
- pregnancy
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 |
|---|---|---|
| Initiation of CFTR ModulatorAlso: 129XeInhaled contrast for MRI occurring at each visit | Drug | CF Cohort |
| Hyperpolarized Xenon 129Also: 129XeInhaled contrast for MRI occurring at each visit | Drug | CF Cohort, Control Cohort |
Primary outcome
Ventilation Defect Percentage (VDP)
Time frame: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Lung defect calculations (total and lobar defect percentages) will be performed by evaluating the percentage of voxels with signals below a threshold value of 60% of the total lung mean signal. This threshold (60%) represents our estimate of the visually accurate defect selection threshold for CF patients. To assign the pixels in the hyperpolarized Xenon gas (129Xe) MRI slices to a lobe, corresponding CT and/or UTE MRI images will be segmented and analyzed with custom MATLAB software. VDP for CF and Control groups will be compared by 2-sample T-test at baseline. VDP at baseline and 6 months for the CF group will be compared by paired T-test to determine if the change is significantly different from zero change.
Perfusion Defect Percentage (PDP)
Time frame: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Similar to the VDP, total and lobar defect percentages will be calculated for lung perfusion. As for VDP, PDP will be compared between CF and Control groups at baseline via 2-sample T-test. PDP change from baseline to 6 months will be measured for the CF group via paired T-test to determine change significantly different from zero change.
Degree of concordance between ventilation and perfusion defects
Time frame: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Degree of concordance between ventilation and perfusion defects will be calculated as percentage of overlap between ventilation and perfusion defect volumes.
Proteome assays as global indicators of inflammatory/angiogenic processes
Time frame: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.
Proteome assays as global indicators of inflammatory/angiogenic processes, will be compared between groups by 2-sample T-test. Correlation analyses will be performed to examine associations between quantitative image scores for each modality (VDP and PDP) and lung function (FEV1%), as well as proteome concentrations.
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 28 Jan 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.
Mark DiFrancesco, PhD principal investigator
CCHMC
Jason Woods, PhD study chair
CCHMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Initiation of CFTR Modulator and Hyperpolarized Xenon 129 in people with Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati 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 10 inclusion and 2 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 28 Jan 2026. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Ventilation Defect Percentage (VDP) (time frame: Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.). The study lists 4 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 28 Jan 2026.