Iron Deficiency in Cystic Fibrosis: Characterization of Clinical Impact and Treatment Effects

PROJECT SUMMARY Shijing Jia, MD, is a Pulmonary and Critical Care physician at the University of Michigan. This K23 mentored career development application includes a coordinated 5-year plan of training and research activities designed to advance Dr. Jia toward her long-term goal of becoming an independent physician-scientist conducting patient-oriented research on cystic fibrosis (CF). CF is a common genetic disorder which has now been described in people of all races and ethnicities. Iron deficiency is a highly prevalent extrapulmonary co- morbidity in CF and is reported to affect 30-80% of those with CF. As observed in other chronic inflammatory disease states with a high prevalence of, like chronic kidney disease (CKD) and inflammatory bowel disease (IBD), ID in CF has been linked to markers of poor clinical outcomes. However, while the CKD and IBD fields each have disease-specific diagnostic and treatment guidelines for ID, which include a low threshold for diagnosis and expeditious treatment via intravenous (IV) repletion, no guidelines exist specific to CF. There is a critical, urgent need to understand clinically meaningful ID as determined by presently available biomarkers and provide data on the clinical efficacy of available ID treatments via IV versus oral repletion therapy. This proposal aims to systemically provide high-impact clinical outcomes data on ID in CF through 1) a multicenter retrospective cohort study; and 2) a prospective two-center randomized pilot study. In completion of this project, Dr. Jia will provide evidence on clinically meaningful diagnostic thresholds for ID in CF using available biomarkers, describe the comparative efficacy and safety of IV and PO iron repletion in CF, and ultimately use these results to power a multicenter randomized trial of ID treatment in CF. The training plan includes intensive mentorship by experts in clinical trials (MeiLan Han, MD and Jennifer Taylor-Cousar, MD, Richard Simon, MD), iron deficiency in CF (Alex Gifford, MD and Angela Weyand, MD), and biostatistics (Susan Murray, ScD), formal coursework to obtain a Master’s Degree in Biostatistics, professional development activities, and progressively independent research. Completion of this stagewise training program will train Dr. Jia to lead future CF trials in subsequent R01, U01, and/or R21 applications. Dr. Jia’s unique resources include access to a dedicated team of co-mentors, advisors, and collaborators with whom she has longstanding relationships. The University of Michigan has an outstanding research infrastructure, actively supports junior investigators, and offers advanced courses and training in relevant disciplines to ensure her future success as an independent investigator.