Admin-Core

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Summary-Administrative Core Peanut allergy (PA) is common, affecting 2-5% of school-age children in the US. The characteristics of PA vary widely among individuals, with some reacting to 1/100th of a peanut and others not having symptoms until they have ingested many peanuts. Symptoms can vary from mild rashes to fatal anaphylaxis. There is no FDA- approved treatment, and all patients with PA are managed with strict allergen avoidance. Most research on PA has focused on those with the most exquisite sensitivity to peanut. Immunotherapy trials commonly exclude subjects with a threshold dose over 1/3 of a peanut (100mg). However, most individuals with PA have higher thresholds of reaction and are excluded from current research approaches. We hypothesize that the natural heterogeneity of PA is a valuable opportunity for investigation. We have shown that milk or egg allergic individuals with tolerance to baked forms of these foods not only tolerate their inclusion in the diet, but this exposure increases the rate of resolution 14-16-fold. We hypothesize that dietary exposure to sub-threshold levels of peanut in those with higher threshold levels of reactivity could lead to significant clinical improvement. Furthermore, studying the natural heterogeneity of PA is a valuable opportunity to elucidate mechanisms of disease. In this center grant, which uses the “Model B: Clinical Trial” format, we build a program around a randomized open feeding trial (CAFETERIA trial, Project 1) to investigate a prototype approach where children with moderate PA (tolerating at least 100 mg of peanut) ingest a sub-threshold amount daily, with increasing levels tested every 3 months. The impact of dietary intervention will be tested at 1 and 2 years by oral food challenge. The trial will be administered by the Clinical Core, which will distribute samples to Projects 2 and 3, for determining the immune and molecular basis of phenotypic heterogeneity in peanut allergy. The Clinical Core will also house the Data and Statistical Coordinating Center (DSCC). The Administrative Core will facilitate this program by providing the administrative and organizational structure for this Center, coordinating interactions within (Projects 1-3 and the Clinical Core) and outside the Center, e.g. with NIAID, other AADCR Centers, and with the external Scientific Advisory Board. The Administrative Core will provide managerial support, organizational support for monthly internal project review meetings, quarterly inter-project meetings of PI's and key personnel, AADCRC Steering Committee teleconferences, Scientific Advisory Board teleconferences/meetings, and annual AADCRC PI meetings in Bethesda. The Core will arrange lodging, meeting rooms and equipment for meetings held at Mount Sinai, take and distribute notes from intra-project and inter-project meetings, and process travel expense reports for scientific meetings and PI, Project PI and Co-PI’s attendance at annual AADCRC meetings. The Core will also work with the AADCRC Steering Committee to promote the sharing of data collected as a part of this proposal and of methods, procedures and resources developed in support of this proposal with other members of the AADCRC network.