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-行政核心 花生过敏（PA）是常见的，影响美国2-5%的学龄儿童。PA的特性各不相同 在个体中广泛存在，有些人对1/100的花生有反应，其他人直到他们吃了花生才出现症状。 吃了很多花生症状可以从轻微的皮疹到致命的过敏反应。没有FDA- 批准的治疗，所有PA患者都严格避免过敏原。关于PA的大多数研究 专注于那些对花生最敏感的人免疫治疗试验通常排除 阈值剂量超过1/3花生（100毫克）的受试者。然而，大多数患有PA的人 反应阈值，并排除在目前的研究方法。我们假设自然的 PA的异质性是研究的宝贵机会。我们已经证明牛奶或鸡蛋过敏 对烘焙形式的这些食物具有耐受性的个体不仅容忍它们被包含在饮食中，而且 曝光将分辨率提高14-16倍。我们假设饮食中暴露于低于阈值的 在那些具有较高阈值水平的反应性的人中，花生水平可以导致显著的临床改善。 此外，研究PA的天然异质性是阐明PA的机制的宝贵机会。 疾病在这个中心补助金中，它使用“模式B：临床试验”的格式，我们围绕一个 随机开放喂养试验（CAFETERIA试验，项目1），以研究一种原型方法，其中儿童 中度PA（耐受至少100 mg花生）每日摄入低于阈值的量， 每3个月测试一次。饮食干预的影响将在第1年和第2年通过口服食物进行测试 挑战.该试验将由临床中心管理，该中心将向项目2和项目3分发样本， 用于确定花生过敏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 通过为该中心提供行政和组织结构，协调 中心内部（项目1-3和临床核心）和外部的互动，例如与NIAID、其他AADCR 中心，并与外部科学顾问委员会。行政核心将提供管理 为每月内部项目审查会议、季度项目间会议、 主要研究者和关键人员、AADCRC指导委员会电话会议、科学顾问委员会 电话会议/会议和在贝塞斯达举行的AADCRC PI年度会议。内核会安排住宿 会议室和设备，用于在西奈山举行的会议，记录和分发项目内部的笔记 和项目间会议，并处理科学会议和PI、项目PI和 共同主要研究者出席亚洲药物滥用和康复中心年度会议。核心还将与AADCRC指导委员会合作 委员会，以促进共享作为本提案的一部分收集的数据以及方法、程序和 与AADCRC网络的其他成员一起开发支持这一建议的资源。