Consortium of Food Allergy Research Clinical Research Center at Cincinnati Children's Hospital Medical Center (CoFAR-CRC:CCHMC) - PROJECT SUMMARY The proposed Consortium of Food Allergy Research Clinical Research Center: Cincinnati Children's Hospital Medical Center (CoFAR-CRC:CCHMC) aims to bring the experience, expertise, and scientific productivity and the diverse patient populations of CCHMC to CoFAR. The patient population seen in the clinics and participating in the research of the Division of Allergy and Immunology at CCHMC encompass varied presentations and classifications of food allergy, including IgE-mediated food allergy (IgE-FA), eosinophilic esophagitis (EoE), and food protein–induced enterocolitis (FPIES). The CoFAR CRC:CCHMC approach to research is multipronged and self-sustaining by attracting patients with excellent care and creating and maintaining databases and registries supported by biospecimen collection and biobanking. Those are utilized in conducting mechanistic research that forms the basis of discoveries and clinical trials and advances knowledge that improves patient care and attracts more patients. The description of the CoFAR CRC:CCHMC will provide a) data on the capacity and readiness of the CRC; b) solid structure and wide range of services available; c) recruitment abilities from the CRC databases and the community, specifically of difficult-to-recruit populations, including minorities, infants, and adults; d) track record of initiation and successful and regulatory- compliant execution of collaborative, multi-center clinical trials; e) support of professional development of faculty and staff; and f) development and inclusion of junior faculty. We propose a network-wide, multicenter clinical trial focused on maintaining acquired tolerance to food allergens and a center-specific research project focused on defining the mechanism by which environmental factors contribute to the pathogenesis of food allergies. For our potential network-wide clinical trial, we hypothesize that the gradual lengthening of the dosing intervals in oral immunotherapy (OIT) in a similar pattern as in allergen immunotherapy protocols or cluster dosing (4 days consecutive dosing + 3-day dosing holiday weekly) will maintain OIT-acquired tolerance as well as daily dosing while providing a more manageable and acceptable dosing schedule for patients and their families. We will conduct a prospective, open, 3-arm, non-inferiority trial of peanut OIT in children 3–8 years of age; the primary outcome is passing an end-of-study (24 months) oral challenge to a serving size of peanut protein. Mechanistic studies of changes in B cell receptors and basophil activation will explore novel biomarkers for assessing long-term tolerance. For our center-specific project, we hypothesize that EoE and IgE-FA are driven by environmental exposures that abrogate the aryl hydrocarbon (AHR) pathway; we propose to investigate the mechanism of AHR function, therapeutic potential of esophageal delivery of AHR ligand- producing bacteria, and metabolic composition of AHR ligands in food allergies, intersecting the AHR ligand composition with cellular and molecular profiles of the epithelium and atopic manifestations.
