Cystic FibrosisNCT02848560
Monitoring Response to Orkambi in Cystic Fibrosis Lung Disease by Inhaled Xenon MRI
An observational study of Cystic Fibrosis, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
This is an observational study for children with Cystic Fibrosis (CF) who are eligible based on their CF gene type. One group will be called the treatment group because they have the gene type (homozygous F508del) that makes them clinically eligible through their CF care provider to begin treatment with the new FDA… Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Hyperpolarized Xenon
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to 31 Oct 2025
- 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 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Study population: Cystic Fibrosis patients naïve to orkambi and with either homozygous F508del CFTR mutation or heterozygous F508del CFTR mutation and pancreatic insufficient.
Who may be able to join
- Treatment group:
- male or female between the ages of 6 through 12 years at enrollment
- two copies of the F508del CFTR mutation
- anticipated to be a candidate for treatment with orkambi
- Control group:
- male or female between the ages of 6 through 12 years at enrollment
- two non-functional CFTR mutations with one of them being F508del CFTR mutation
- not eligible for CFTR modulation therapy
Who cannot join
- FEV1 percent predicted of <60%
- 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
Official title: Validation of MRI as a Sensitive Tool to Longitudinally Monitor CF Lung Disease Progression and Response to CFTR Modulator Therapy in Young Children With CF
This is an observational study for children with Cystic Fibrosis (CF) who are eligible based on their CF gene type. One group will be called the treatment group because they have the gene type (homozygous F508del) that makes them clinically eligible through their CF care provider to begin treatment with the new FDA approved CF drug called orkambi. For the control group, children will be enrolled who have a similar CF gene type (heterozygous F508del) but are not eligible to be prescribed orkambi.
The two groups will be followed for four visits over about 3 to 4 years to observe changes in the lungs. Methods to measure the changes in lung disease will include:
Read more
MRI with non-FDA approved inhaled xenon gas to take detailed images of the lungs, Pulmonary Function Tests (PFT), Lung Clearance Index (LCI), Baseline CT image of the lungs if not ordered as part of usual clinical care.
The first two visits will be done before starting clinical treatment with orkambi and will be a minimum of 28 days apart and up to 18 months. The third visit will be scheduled about 3 months after starting orkambi and the fourth visit about 18 months later. For the control group, the timing of visits will be similar to treatment group and visits may be scheduled around annual CF care visits.
Read the detailed description
This is a controlled observational longitudinal study designed to capture Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapy naive Cystic Fibrosis (CF) subjects with F508del(+/+) mutations before they age into the FDA approved treatment window for the CFTR modulator orkambi (ivacaftor/lumacaftor). These subjects will be compared to disease controls. The treatment group will be observed twice (at least 28 days apart and up to 18 months) before clinically starting orkambi and observed twice (at about 3 months and about 18 months) after clinically starting orkambi .
This study takes advantage of the timely development of Ultrashort Echo Time Magnetic Resonance Imaging (UTE MRI), Hyperpolarized Xenon (129Xe) MRI, Lung Clearance Index (LCI), and the approval of F508del CFTR-directed CF therapy in children. The proposal will:
- validate the emerging biomarker (UTE MRI) within CF children independent of genotype, ii) define the trajectory of UTE MRI and forced expiratory volume in 1 second (FEV1) changes before and after initiating orkambi therapy compared with age-matched CF controls, and iii) determine the relationships between regional structural abnormalities (UTE MRI) and regional (129Xe MRI) and global (LCI) functional measures of ventilation. Results will establish MRI as a sensitive lung imaging tool that is translatable to all CF centers and can be applied throughout the lifespan of CF patients.
CF patients with one or two copies of the F508del CFTR mutation who are 6-12 years old will undergo UTE MRI soon after a clinical computerized tomography (CT) scan, with disease quantification using an established scoring system for both modalities. Quantitative imaging data and LCI will be compared with spirometry (gold standard for CF lung disease) and clinical predictors of disease progression.
The F508del(+/+) patient cohort will differ genotypically from the control cohort (F508del[+/-]). All patients in the F508del(+/-) cohort will be pancreatic insufficient and also have a nonfunctional second allele (Class I or II mutation, not candidates for modulator therapy). These two cohorts are phenotypically indistinguishable without modulator treatment, and therefore the untreated cohort will serve as an ideal age and time-matched control group for the F508del(+/+) subjects who clinically initiate orkambi.
Disease trajectories in the two groups, as quantified by changes in pulmonary UTE MRI, will be compared with FEV1. MRI analysis will include quantitative and reader-based "Brody" scoring for the whole lung, lung lobes, and for subcategories of the Brody scoring system (in particular bronchiectasis, bronchial wall thickening, and mucus plugging).
The longitudinal study will capture both cohorts at their scheduled annual CF visits when possible over about 4 years with modifications to the timeline for the treatment group based on when they are clinically scheduled to begin orkambi treatment.
As FDA approved indications for orkambi change, subjects in the F508del(+/+) cohort will become candidates for modulators prior to their 12th birthday. The FDA is currently reviewing for approval in Fall 2016 to lower the prescribing age to 6 years and the investigators will be enrolling to meet the changes at that time.
- Conditions
- Cystic Fibrosis
- Being tested
- Hyperpolarized Xenon
- Keywords
- Cystic Fibrosis, orkambi, 129Xe MRI, hyperpolarized xenon, LCI, CFTR modulator therapy
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperpolarized XenonDrug
Also called 129Xe
Inhaled contrast for MRI occurring at each of 4 visits.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Observation of lung changes over time by hyperpolarized xenon MRI on CF patients homozygous for F508del CFTR mutation as they age into the FDA approved treatment window for the CFTR modulator orkambi. Subjects will be observed at 2 time points before starting clinically prescribed treatment (orkambi) and 2 time points while on orkambi. Receives: Drug: Hyperpolarized Xenon | |
| Control | Observation of lung changes over time by hyperpolarized xenon MRI on CF patients heterozygous for F508del CFTR mutation at similar timepoints to treatment group. Control subjects are not be eligible to be clinically prescribed orkambi based on FDA approval. Receives: Drug: Hyperpolarized Xenon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hyperpolarized 129Xe MRI Image Analysis
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.
Measured: Visit 4 (year 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study startMar 2016
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Oct 2025 (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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jason Woods, Children's Hospital Medical Center, Cincinnati
- Investigators
- Jason Woods, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02848560
- Sponsor's protocol ID
- CINOO1-CF Orkambi and Xe MRI
- Other IDs
- 1R01HL131012-01A1
- Status last verified
- Nov 2024
- First submitted
- 26 Jul 2016
- Last updated
- 21 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: MRI results will be shared with treating CF physicians to support clinical decisions.
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of MRI as a Sensitive Tool to Longitudinally Monitor CF Lung Disease Progression and Response to CFTR Modulator Therapy in Young Children With CF
- ClinicalTrials.gov ID
- NCT02848560
- Acronym / sponsor ID
- CINOO1-CF Orkambi and Xe MRI
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, orkambi, 129Xe MRI, hyperpolarized xenon, LCI, CFTR modulator therapy
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2016 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Oct 2025 (estimated)
- First posted
- 28 Jul 2016 (estimated)
- 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.
This is an observational study for children with Cystic Fibrosis (CF) who are eligible based on their CF gene type. One group will be called the treatment group because they have the gene type (homozygous F508del) that makes them clinically eligible through their CF care provider to begin treatment with the new FDA approved CF drug called orkambi. For the control group, children will be enrolled who have a similar CF gene type (heterozygous F508del) but are not eligible to be prescribed orkambi.
The two groups will be followed for four visits over about 3 to 4 years to observe changes in the lungs. Methods to measure the changes in lung disease will include:
MRI with non-FDA approved inhaled xenon gas to take detailed images of the lungs, Pulmonary Function Tests (PFT), Lung Clearance Index (LCI), Baseline CT image of the lungs if not ordered as part of usual clinical care.
The first two visits will be done before starting clinical treatment with orkambi and will be a minimum of 28 days apart and up to 18 months. The third visit will be scheduled about 3 months after starting orkambi and the fourth visit about 18 months later. For the control group, the timing of visits will be similar to treatment group and visits may be scheduled around annual CF care visits.
Detailed description
This is a controlled observational longitudinal study designed to capture Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapy naive Cystic Fibrosis (CF) subjects with F508del(+/+) mutations before they age into the FDA approved treatment window for the CFTR modulator orkambi (ivacaftor/lumacaftor). These subjects will be compared to disease controls. The treatment group will be observed twice (at least 28 days apart and up to 18 months) before clinically starting orkambi and observed twice (at about 3 months and about 18 months) after clinically starting orkambi .
This study takes advantage of the timely development of Ultrashort Echo Time Magnetic Resonance Imaging (UTE MRI), Hyperpolarized Xenon (129Xe) MRI, Lung Clearance Index (LCI), and the approval of F508del CFTR-directed CF therapy in children. The proposal will:
- validate the emerging biomarker (UTE MRI) within CF children independent of genotype, ii) define the trajectory of UTE MRI and forced expiratory volume in 1 second (FEV1) changes before and after initiating orkambi therapy compared with age-matched CF controls, and iii) determine the relationships between regional structural abnormalities (UTE MRI) and regional (129Xe MRI) and global (LCI) functional measures of ventilation. Results will establish MRI as a sensitive lung imaging tool that is translatable to all CF centers and can be applied throughout the lifespan of CF patients.
CF patients with one or two copies of the F508del CFTR mutation who are 6-12 years old will undergo UTE MRI soon after a clinical computerized tomography (CT) scan, with disease quantification using an established scoring system for both modalities. Quantitative imaging data and LCI will be compared with spirometry (gold standard for CF lung disease) and clinical predictors of disease progression.
The F508del(+/+) patient cohort will differ genotypically from the control cohort (F508del[+/-]). All patients in the F508del(+/-) cohort will be pancreatic insufficient and also have a nonfunctional second allele (Class I or II mutation, not candidates for modulator therapy). These two cohorts are phenotypically indistinguishable without modulator treatment, and therefore the untreated cohort will serve as an ideal age and time-matched control group for the F508del(+/+) subjects who clinically initiate orkambi.
Disease trajectories in the two groups, as quantified by changes in pulmonary UTE MRI, will be compared with FEV1. MRI analysis will include quantitative and reader-based "Brody" scoring for the whole lung, lung lobes, and for subcategories of the Brody scoring system (in particular bronchiectasis, bronchial wall thickening, and mucus plugging).
The longitudinal study will capture both cohorts at their scheduled annual CF visits when possible over about 4 years with modifications to the timeline for the treatment group based on when they are clinically scheduled to begin orkambi treatment.
As FDA approved indications for orkambi change, subjects in the F508del(+/+) cohort will become candidates for modulators prior to their 12th birthday. The FDA is currently reviewing for approval in Fall 2016 to lower the prescribing age to 6 years and the investigators will be enrolling to meet the changes at that time.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | – | Drug: Hyperpolarized XenonObservation of lung changes over time by hyperpolarized xenon MRI on CF patients homozygous for F508del CFTR mutation as they age into the FDA approved treatment window for the CFTR modulator orkambi. Subjects will be observed at 2 time points before starting clinically prescribed treatment (orkambi) and 2 time points while on orkambi. |
| Control | – | Drug: Hyperpolarized XenonObservation of lung changes over time by hyperpolarized xenon MRI on CF patients heterozygous for F508del CFTR mutation at similar timepoints to treatment group. Control subjects are not be eligible to be clinically prescribed orkambi based on FDA approval. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Cystic Fibrosis patients naïve to orkambi and with either homozygous F508del CFTR mutation or heterozygous F508del CFTR mutation and pancreatic insufficient.
Key inclusion criteria (8 listed)
- male or female between the ages of 6 through 12 years at enrollment
- two copies of the F508del CFTR mutation
- anticipated to be a candidate for treatment with orkambi
- male or female between the ages of 6 through 12 years at enrollment
- two non-functional CFTR mutations with one of them being F508del CFTR mutation
Key exclusion criteria (3 listed)
- FEV1 percent predicted of <60%
- 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 |
|---|---|---|
| Hyperpolarized XenonAlso: 129XeInhaled contrast for MRI occurring at each of 4 visits. | Drug | Control, Treatment |
Primary outcome
Hyperpolarized 129Xe MRI Image Analysis
Time frame: Visit 4 (year 3)
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.
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 21 Nov 2024.
- Individual participant dataSharing planned: Yes. MRI results will be shared with treating CF physicians to support clinical decisions.
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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.
Jason Woods, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site 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 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 3 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 21 Nov 2024. 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.
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?
Hyperpolarized 129Xe MRI Image Analysis (time frame: Visit 4 (year 3)). 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 21 Nov 2024.