The introduction of triple combination CFTR modulator therapy for patients with Cystic
Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major
health benefits, but will also require novel outcome measures that can detect CF lung disease
at an early stage, capture the efficacy of new therapies when disease manifestations are
limited, as well as determine whether stopping existing chronic maintenance therapies does
not have negative effects.
In the past decade, research has focused on the multiple breath washout (MBW) test, as a
sensitive outcome measure, especially if highly-effective modulator therapies are initiated
in early childhood. Even LCI, however, may not adequately capture early lung function
changes, thus warranting investigation of even more sensitive outcome measures.
Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making
it more suitable for assessing response to therapy in a shorter time frame with repeated
imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of
regional ventilation in the lung and can be combined with structural MRI to assess both
structure and function in parallel.
The main Investigator and others have recently formed an international consortium (the 129Xe
MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to
standardize imaging procedures, thus facilitating multi-site implementations. Data from this
proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future
utility of MRI for both longitudinal studies to track disease progression over time as well
as for future interventional trials. Further, the current study could inform the design of
future trials of interventions of patients for whom currently no effective CFTR modulator
therapy is available and for patients with rare genotypes thus laying the groundwork for a
more personalized medicine approach in the near-term future.
Phase:
Phase 4
Details
Lead Sponsor:
Children's Hospital Medical Center, Cincinnati
Collaborators:
The Hospital for Sick Children University of Virginia University of Wisconsin, Madison