Hyperpolarized Imaging for New Treatments (HyPOINT)
Cystic Fibrosis
About this trial
This is an interventional diagnostic trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, CFTR modulator therapy, 129Xe MRI, hyperpolarized xenon, LCI
Eligibility Criteria
Inclusion Criteria:
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
- Willingness and ability to adhere to the study visit schedule and other protocol requirements.
Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
- Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test
- Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
- Phase 1 only: Age 6 to 18 years, inclusive, at the time of consent.
- Phase 2 only: Ages 9 to 18 years, inclusive, at the time of consent.
- Clinically stable with no acute antibiotic usage in the 14 days prior to the first visit.
- Genotype with F508del on at least one allele.
- No change in chronic pulmonary medications or therapies in the 28 days prior to the first visit.
- Stable CFTR modulator therapy (TEZ/IVA or LUM/IVA) for at least 28 days prior to the first visit or currently not receiving CFTR modulator therapy.
- Ability to cooperate with MRI procedures.
- Phase 1 only: FEV1 greater than or equal to 80% predicted based on GLI reference equations.
Exclusion Criteria:
- Standard MRI exclusions (Metal implants, claustrophobia).
- For females of childbearing potential: Positive urine pregnancy test at Screening or Visit 1 or Lactating.
- Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Sites / Locations
- Cincinnati Children's Hospital Medical Center
- University of Virginia School of Medicine
- University of Wisconsin
- The Hospital for Sick Kids
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Phase 1
Initiation of CFTR Modulator
Phase 1 will include implementation of a centralized analysis program of repeated 129Xe MRI scanning in CF patients with mild lung disease to define the intra-subject variability of the primary outcome ventilation defect percentage (VDP). Patients will undergo baseline 129Xe MRI scanning and repeated measurements the same day, as well as at 28 days (± 7 days). Phase 1 will establish the intra-subject reproducibility to facilitate future use of 129Xe MRI in multi-site studies. Furthermore, the reproducibility limits defined will inform the overall design of future studies and will compare to established pulmonary function and multiple-breath washout testing (via measurement of the lung clearance index, LCI).
Phase 2 will be an observational study of patients assessed before and after the clinical initiation of triple-combination modulator therapy (after presumed FDA and Health Canada approval). The primary endpoint for Phase 2 is the change of VDP after 28 days of triple-combination modulator therapy. Within Phase 2, this study will also address how highly-effective modulator therapies affect lung function trajectories by measuring 129Xe MRI at 28 days (± 7 days), 6 months (± 28 days), and 12 months (± 28 days) after start of therapy (paralleling time points of the PROMISE study). Finally, to understand how 129Xe MRI can be used in combination with existing measures of lung function (e.g. spirometry, multiple breath washout), the investigators will directly compare the repeated data collected in both Phase 1 and Phase 2 to these established measures of lung function that are currently used in observational and interventional studies.