Admin-Core

管理核心

• 批准号: 10415889
• 负责人: Maria CECILIA BERIN
• 金额: $ 8.62万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-06 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415889
• 关键词: Affect; Allergens; Allergic; Allergic Disease; Allergy to eggs; Allergy to peanuts; Anaphylaxis; Arachis hypogaea; Asthma; Biological Markers; Characteristics; Child; Clinical; Clinical Trials; Communication; Data; Diet; Dietary Intervention; Disease; Disease Outcome; Dose; Epinephrine; Equipment; Exanthema; Exposure to; FDA approved; Food; Food Hypersensitivity; Grant; Heart; Heterogeneity; Human Resources; Immune; Individual; Ingestion; Investigation; Lead; Link; Methods; Milk; Milk Hypersensitivity; Modeling; Molecular; National Institute of Allergy and Infectious Disease; Oral; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Population; Procedures; Process; Quality of life; Randomized; Randomized Clinical Trials; Reaction; Reporting; Research; Resolution; Resources; Review Committee; Sampling; School-Age Population; Specimen; Speed; Symptoms; Teleconferences; Testing; Travel; Work; base; cost; data communication; data sharing; dietary; economic impact; egg; feeding; food challenge; high dimensionality; immunotherapy trials; improved; meetings; member; organizational structure; programs; prototype; transcriptome sequencing

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.

摘要 - 管理核心 花生过敏（PA）很常见，影响了美国2-5％的学龄儿童。 PA品种的特征 在个人中广泛，有些人对1/100的花生有反应，而其他人则没有符号 摄取了许多花生。症状可能从轻度皮疹到致命的过敏反应。没有FDA- 经过批准的治疗，所有患有PA的患者均受到严格避免过敏原的治疗。关于PA的大多数研究 专注于对花生敏感最敏感的人。免疫疗法试验通常排除 阈值剂量超过1/3花生（100mg）的受试者。但是，大多数患有PA的人都更高 反应的阈值，被排除在当前的研究方法之外。我们假设自然 PA的异质性是投资的宝贵机会。我们已经表明牛奶或鸡蛋过敏 对这些食物的烘焙形式耐受性的人不仅可以容忍饮食中的包容，而且还可以 暴露量增加了14-16倍的分辨率。我们假设饮食暴露于亚阈值 反应性阈值水平较高的花生水平可能会导致显着的临床改善。 此外，研究PA的自然异质性是阐明机制的宝贵机会 疾病。在使用“ B：临床试验”格式的此中心赠款中，我们围绕A构建了一个程序 随机开放式喂养试验（自助餐厅试验，项目1）调查儿童的原型方法 每天摄取中等PA（至少100毫克花生）每天摄入亚阈值数量，随着增加的数量 每3个月测试水平。饮食干预的影响将在1年和2年的口腔食品中测试 挑战。该试验将由临床核心管理，该临床核心将向项目2和3分配样品， 用于确定花生过敏中表型异质性的免疫和分子基础。临床 核心还将容纳数据和统计协调中心（DSCC）。行政核心将 通过提供该中心的行政和组织结构来促进该计划，并协调 （项目1-3和临床核心）和中心之外的相互作用，例如与niaid，其他AADCR 中心以及外部科学顾问委员会。行政核心将提供管理 支持，组织每月内部项目审查会议的组织支持，季度项目间会议 PI和关键人物，AADCRC指导委员会电视会议，科学顾问委员会 电信/会议和贝塞斯达的年度AADCRC PI会议。核心将安排住宿， 会议室和设备，用于在西奈山举行的会议，从项目内获取并分发笔记 以及项目间会议，以及科学会议和PI，Project PI和 Co-Pi参加年度AADCRC会议。核心也将与AADCRC转向一起使用 促进作为本提案以及方法，程序和方法的一部分收集的数据共享的委员会 为支持AADCRC网络的其他成员支持该提案而开发的资源。