Cystic FibrosisEarly Phase 1NCT03497117
19F MRI of Ventilation in Subjects With Cystic Fibrosis Undergoing Treatment for Pulmonary Exacerbation
A Early Phase 1 study testing Lung Clearance Index and MRI with PFP in people with Cystic Fibrosis, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to use perfluorinated gas imaging to highlight regions of functional variation within the lungs of participants with cystic fibrosis (CF), and to correlate this with changes in spirometry, lung clearance index, and quality of life of CF subjects undergoing treatment for a pulmonary… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Lung Clearance Index and MRI with PFP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Aug 2015to 13 Sep 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-smokers (<10 pack year history and no active smoking in the past year);
- Diagnosis of cystic fibrosis via standard sweat chloride/phenotypic features/genotyping
- Able to reproducibly perform lung function testing and have an FEV1 >30% of predicted at screening.
- No requirement for supplemental oxygen
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
- Participants must be willing and able to comply with scheduled visits and other trial procedures.
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- Diagnosis of a pulmonary exacerbation according to Fuchs criteria (4 of the following 12 signs and symptoms) deemed to require antibiotic treatment, and must also include the change in lung function criterion:
- Change in sputum
- New or increased hemoptysis
- Increased cough
- Increased dyspnea
- Malaise, fatigue, or lethargy
- Temperature above 38deg C
- Anorexia or weight loss
- Sinus pain or tenderness
- Change in sinus discharge
- Change in physical examination of the chest
- Decrease in pulmonary function by 10% or more from a previously recorded value
- Radiographic change indicative of pulmonary infection
Who cannot join
- Under 18 years of age
- Active or former smokers with less than 1 years since quitting, or >10 pack-year smoking history
- Active asthma flare, as perceived by the study physician or unstable asthma characterized by advancement of asthma therapy in the last month or two courses of oral steroids in the past six months.
- Unable to undergo a 3.0-Tesla MRI of lungs and chest because of contraindications including
- Occupation (past or present) of machinist, welder, grinder
- Injury to the eye involving a metallic object
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- Injury to the body by a metallic object (bullet, BB, shrapnel)
- Presence of a cardiac pacemaker or defibrillator
- Presence of aneurysm clips
- Presence of carotid artery vascular clamp
- Presence of neurostimulator
- Presence of insulin or infusion pump
- Presence of implanted drug infusion device that is not known to be MRI compatible (i.e., was placed outside of University of North Carolina Hospitals (UNCH) or is older than 10 years)
- Bone growth or fusion simulator
- Presence of cochlear, otologic or ear implant
- Any type of prosthesis (eye, penile, etc.)
- Artificial limb or joint
- Non-removable electrodes (on body, head or brain)
- Intravascular stents, filters or coils
- Shunt (spinal or intraventricular)
- Swan-Ganz catheter
- Any implant held in place by a magnet
- Transdermal delivery system (e.g. Nitro)
- Intrauterine device (IUD) or diaphragm
- Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface area
- Body piercings (MUST BE REMOVED BEFORE MRI)
- Any metal fragments
- Internal pacing wires
- Metal or wire mesh implants
- Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb. Claustrophobia
- Unable to tolerate inhalation of the gas mixture
- Unable to adequately complete other study measures, including spirometry and multiple breath nitrogen washout
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or may interfere with the interpretation of trial results and, in the judgment of the PI, would make the participant inappropriate for enrollment.
- Pregnancy; women of childbearing potential must have a confirmed negative serum pregnancy test at screening, and a negative urine test on the day of the MRI scan, prior to the MRI scan (if serum test not performed the same day).
- Facial hair preventing a tight fit of the mask used in the study
- Allergy or intolerance due to side effects to bronchodilators
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: 19F Magnetic Resonance Imaging of Ventilation in Subjects With Cystic Fibrosis Undergoing Treatment for Pulmonary Exacerbation
The purpose of this study is to use perfluorinated gas imaging to highlight regions of functional variation within the lungs of participants with cystic fibrosis (CF), and to correlate this with changes in spirometry, lung clearance index, and quality of life of CF subjects undergoing treatment for a pulmonary exacerbation.
Read the detailed description
The investigators hypothesize that 19F-enhanced MRI will detect improvements in lung ventilation following the treatment of a CF pulmonary exacerbation, and changes in ventilation as well as global MRI scores will track with both spirometry and quality of life assessments. Therefore, investigators propose this pilot and feasibility study to gain preliminary data on a comparison of the changes in ventilation that occur with treatment of a pulmonary exacerbation, as well as to begin to understand the repeatability of this novel outcome measure. Through this study, the investigators aim to: 1) Compare quantitative and qualitative assessments of lung ventilation using 19F MRI imaging and traditional, global physiologic assessments (spirometry, LCI) and compare these with images obtained in an age-matched healthy control population; 2) Correlate changes in MRI scoring with subjective changes in health related outcomes as measured by the CFQ-R (Cystic Fibrosis Questionnaire - Revised); 3) Determine the ability of 19F MRI to detect changes in ventilation that occur with treatment of a CF pulmonary exacerbation; and 4) Determine the repeatability of 19F MRI assessment of ventilation in a disease population.
Participants with CF with baseline forced expiratory volume in 1 second (FEV1) of at least 40%, no contraindications to MRI, and oxygen saturation >90% on room air will be prospectively enrolled. Investigators will recruit a pre-defined cross-section of CF patients with mild, moderate, and severe lung disease, with approximately 4 subjects per group at the onset of a disease exacerbation requiring antibiotic intervention. The research team will obtain a pre-response MRI (within 3 days of initiating oral, inhaled, or IV antibiotic therapy), and a post-treatment MRI (within 3 days of terminating antibiotic treatment) to assess the responsiveness of 19F-MRI to a change in disease status. Each 19F-MRI study will be combined with assessments of spirometry, LCI (multiple breath nitrogen washout), and quality of life (CFQ-R quality of life tool).
19F-MRI will be performed by having each participant inhale a mixture of 79% perfluorinated propane (PFP) and 21% oxygen (pre-mixed) while using MRI to obtain 3D images. Subsequently, participants will be switched to room air, and cycled breathing will be continued while additional MRI images are captured to characterize gas wash-out. Safety measures, including pulse oximetry, will be monitored continuously, and spirometry will be performed before and after each MRI. Participants will also perform multiple breath washout maneuvers to obtain a lung clearance index, so this may be correlated to wash-out kinetics of the PFP.
- Conditions
- Cystic Fibrosis
- Being tested
- Lung Clearance Index, MRI with PFP
- Keywords
- imaging, hyperpolarized, perfluorinated, MRI, lung, multiple breath washout, lung clearance index
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung Clearance IndexDevice
Also called LCI
To assess the efficiency of ventilation distribution and gas mixing by measuring the rate of clearance of an inert gas (nitrogen) from the lungs.
MRI with PFPDrug
Also called Perfluoropropane gas (C3F8); 19F
- Description: inhaled PFP, a gaseous contrast agent (79% PFP, 21% O2, pre-mixed, medical grade gas)
- Administration: Full-face disposable ventilation mask and a standard Douglas Bag system.
- Dosage: Two controlled breaths of contrast gas followed by a full breath and a 12-second breath-hold and scan for image acquisition.
- Frequency: Repeated 5 times followed by an identical five cycles with room air to ensure PFP gas wash-out has occurred.
| Study group | Role | What they receive |
|---|---|---|
| CF pulmonary exacerbation group | Other | Patients with cystic fibrosis being treated for a pulmonary exacerbation will undergo Lung Clearance Index (LCI) and an MRI with PFP.
LCI testing will take place before the MRI. Each test will take 5-20 minutes and up to three tests will be performed with at least 5-minute rest periods between each test.
PFP gas will be administered using a full-face mask during the MRI. Images are acquired during 12-second breath-hold after every 3rd breath. Before and after the MRI is complete, participants will perform spirometry maneuvers in a room outside of the magnet. Receives: Device: Lung Clearance Index; Drug: MRI with PFP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole lung ventilation defect volume (VDV)
To obtain ventilation defect volumes (VDVs), investigators will use the final wash-in image to identify all regions of interest having a signal intensity below the pre-defined threshold which indicates poor ventilation. The combined volume of all these 'ventilation defect' regions will be computed to obtain the VDV.
Measured: 1 day
Secondary outcomes (3)
The wash-in kinetics of PFP
For each participant, an exponential model will be fit to obtain a statistical estimate, T, of the rate constant that characterizes the kinetics of gas wash-in. Aggregating across all participants, the frequency distributions of T values will be characterized by tabulating estimates of the mean and standard deviation (SD). Corresponding 95% confidence intervals and the minimum, maximum, and interquartile range of T values will also be tabulated.
Measured: 1 day
Ventilation defect percent (VDP) correlation with LCI
Changes in VDP from pre/post treatment will be correlated with changes in LCI pre- and post-exacerbation.
Measured: 1 day
Ventilation defect percent (VDP) correlation with FEV1
Changes in VDP from pre/post treatment will be correlated with changes in FEV1 pre- and post- exacerbation.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start25 Aug 2015
- Primary completion13 Sep 2019
- Study completion13 Sep 2019
Why it stopped: Enrollment barriers made study completion impossible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants undergoing treatment for a pulmonary exacerbation will perform multiple breath washout and undergo an MRI with inhalation of a gas contrast agent (79% perfluoropropane (PFP) mixed with 21% oxygen) at the beginning and end of treatment.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer Goralski, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03497117
- Sponsor's protocol ID
- 15-0239
- Other IDs
- 2P30DK065988-11
- Status last verified
- Oct 2020
- First submitted
- 29 Mar 2018
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Halaweish AF, Moon RE, Foster WM, Soher BJ, McAdams HP, MacFall JR, Ainslie MD, MacIntyre NR, Charles HC. Perfluoropropane gas as a magnetic resonance lung imaging contrast agent in humans. Chest. 2013 Oct;144(4):1300-1310. doi: 10.1378/chest.12-2597.
PubMed 23722696Couch MJ, Ball IK, Li T, Fox MS, Littlefield SL, Biman B, Albert MS. Pulmonary ultrashort echo time 19F MR imaging with inhaled fluorinated gas mixtures in healthy volunteers: feasibility. Radiology. 2013 Dec;269(3):903-9. doi: 10.1148/radiol.13130609. Epub 2013 Oct 28.
PubMed 23985278
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 19F Magnetic Resonance Imaging of Ventilation in Subjects With Cystic Fibrosis Undergoing Treatment for Pulmonary Exacerbation
- ClinicalTrials.gov ID
- NCT03497117
- Acronym / sponsor ID
- 15-0239
- Conditions
- Cystic Fibrosis
- Keywords
- imaging, hyperpolarized, perfluorinated, MRI, lung, multiple breath washout, lung clearance index
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment barriers made study completion impossible
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 25 Aug 2015 (actual)
- Primary completion
- 13 Sep 2019 (actual)
- Study completion
- 13 Sep 2019 (actual)
- First posted
- 13 Apr 2018 (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.
The purpose of this study is to use perfluorinated gas imaging to highlight regions of functional variation within the lungs of participants with cystic fibrosis (CF), and to correlate this with changes in spirometry, lung clearance index, and quality of life of CF subjects undergoing treatment for a pulmonary exacerbation.
Detailed description
The investigators hypothesize that 19F-enhanced MRI will detect improvements in lung ventilation following the treatment of a CF pulmonary exacerbation, and changes in ventilation as well as global MRI scores will track with both spirometry and quality of life assessments. Therefore, investigators propose this pilot and feasibility study to gain preliminary data on a comparison of the changes in ventilation that occur with treatment of a pulmonary exacerbation, as well as to begin to understand the repeatability of this novel outcome measure. Through this study, the investigators aim to: 1) Compare quantitative and qualitative assessments of lung ventilation using 19F MRI imaging and traditional, global physiologic assessments (spirometry, LCI) and compare these with images obtained in an age-matched healthy control population; 2) Correlate changes in MRI scoring with subjective changes in health related outcomes as measured by the CFQ-R (Cystic Fibrosis Questionnaire - Revised); 3) Determine the ability of 19F MRI to detect changes in ventilation that occur with treatment of a CF pulmonary exacerbation; and 4) Determine the repeatability of 19F MRI assessment of ventilation in a disease population.
Participants with CF with baseline forced expiratory volume in 1 second (FEV1) of at least 40%, no contraindications to MRI, and oxygen saturation >90% on room air will be prospectively enrolled. Investigators will recruit a pre-defined cross-section of CF patients with mild, moderate, and severe lung disease, with approximately 4 subjects per group at the onset of a disease exacerbation requiring antibiotic intervention. The research team will obtain a pre-response MRI (within 3 days of initiating oral, inhaled, or IV antibiotic therapy), and a post-treatment MRI (within 3 days of terminating antibiotic treatment) to assess the responsiveness of 19F-MRI to a change in disease status. Each 19F-MRI study will be combined with assessments of spirometry, LCI (multiple breath nitrogen washout), and quality of life (CFQ-R quality of life tool).
19F-MRI will be performed by having each participant inhale a mixture of 79% perfluorinated propane (PFP) and 21% oxygen (pre-mixed) while using MRI to obtain 3D images. Subsequently, participants will be switched to room air, and cycled breathing will be continued while additional MRI images are captured to characterize gas wash-out. Safety measures, including pulse oximetry, will be monitored continuously, and spirometry will be performed before and after each MRI. Participants will also perform multiple breath washout maneuvers to obtain a lung clearance index, so this may be correlated to wash-out kinetics of the PFP.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants undergoing treatment for a pulmonary exacerbation will perform multiple breath washout and undergo an MRI with inhalation of a gas contrast agent (79% perfluoropropane (PFP) mixed with 21% oxygen) at the beginning and end of treatment.
| Arm | Type | Receives |
|---|---|---|
| CF pulmonary exacerbation group | Other | Device: Lung Clearance Index, Drug: MRI with PFPPatients with cystic fibrosis being treated for a pulmonary exacerbation will undergo Lung Clearance Index (LCI) and an MRI with PFP. LCI testing will take place before the MRI. Each test will take 5-20 minutes and up to three tests will be performed with at least 5-minute rest periods between each test. PFP gas will be administered using a full-face mask during the MRI. Images are acquired during 12-second breath-hold after every 3rd breath. Before and after the MRI is complete, participants will perform spirometry maneuvers in a room outside of the magnet. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Non-smokers (<10 pack year history and no active smoking in the past year);
- Diagnosis of cystic fibrosis via standard sweat chloride/phenotypic features/genotyping
- Able to reproducibly perform lung function testing and have an FEV1 >30% of predicted at screening.
- No requirement for supplemental oxygen
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
Key exclusion criteria (36 listed)
- Under 18 years of age
- Active or former smokers with less than 1 years since quitting, or >10 pack-year smoking history
- Active asthma flare, as perceived by the study physician or unstable asthma characterized by advancement of asthma therapy in the last month or two courses of oral steroids in the past six months.
- Unable to undergo a 3.0-Tesla MRI of lungs and chest because of contraindications including
- Unable to tolerate inhalation of the gas mixture
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 |
|---|---|---|
| Lung Clearance IndexAlso: LCITo assess the efficiency of ventilation distribution and gas mixing by measuring the rate of clearance of an inert gas (nitrogen) from the lungs. | Device | CF pulmonary exacerbation group |
| MRI with PFPAlso: Perfluoropropane gas (C3F8); 19F* Description: inhaled PFP, a gaseous contrast agent (79% PFP, 21% O2, pre-mixed, medical grade gas) * Administration: Full-face disposable ventilation mask and a standard Douglas Bag system. * Dosage: Two controlled breaths of contrast gas followed by a full breath and a 12-second breath-hold and scan for image acquisition. * Frequency: Repeated 5 times followed by an identical five cycles with room air to ensure PFP gas wash-out has occurred. | Drug | CF pulmonary exacerbation group |
Primary outcome
Whole lung ventilation defect volume (VDV)
Time frame: 1 day
To obtain ventilation defect volumes (VDVs), investigators will use the final wash-in image to identify all regions of interest having a signal intensity below the pre-defined threshold which indicates poor ventilation. The combined volume of all these 'ventilation defect' regions will be computed to obtain the VDV.
3 secondary outcomes
The wash-in kinetics of PFP
Time frame: 1 day
Ventilation defect percent (VDP) correlation with LCI
Time frame: 1 day
Ventilation defect percent (VDP) correlation with FEV1
Time frame: 1 day
Results and safety
The study was stopped early (reason given: Enrollment barriers made study completion impossible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Background: PubMed 23722696Halaweish AF, Moon RE, Foster WM, Soher BJ, McAdams HP, MacFall JR, Ainslie MD, MacIntyre NR, Charles HC. Perfluoropropane gas as a magnetic resonance lung imaging contrast agent in humans. Chest. 2013 Oct;144(4):1300-1310. doi: 10.1378/chest.12-2597.
- Background: PubMed 23985278Couch MJ, Ball IK, Li T, Fox MS, Littlefield SL, Biman B, Albert MS. Pulmonary ultrashort echo time 19F MR imaging with inhaled fluorinated gas mixtures in healthy volunteers: feasibility. Radiology. 2013 Dec;269(3):903-9. doi: 10.1148/radiol.13130609. Epub 2013 Oct 28.
- 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 Goralski, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Lung Clearance Index and MRI with PFP in people with Cystic Fibrosis, run by University of North Carolina, Chapel Hill 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 19 inclusion and 36 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: stopped early, as of the sponsor's last update on 9 Oct 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Enrollment barriers made study completion impossible). Results are not available in the source record.
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?
Whole lung ventilation defect volume (VDV) (time frame: 1 day). 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 NCT03497117, 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 9 Oct 2020.