Clinical Research Unit: Johns Hopkins University

临床研究单位：约翰霍普金斯大学

• 批准号: 9307452
• 负责人: ROBERT A WOOD
• 金额: $ 23.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-03 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307452
• 关键词: Adolescence; Adolescent; Adult; Affect; Age; Allergic; Allergy to peanuts; Biological Markers; Birth; Charge; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Collaborations; Communication; Databases; Development; Double-Blind Method; Early treatment; Enrollment; Food; Food Hypersensitivity; Funding; Funding Opportunities; Future; Goals; Health; Hypersensitivity; Immunologic Factors; Immunologics; Immunology; Immunotherapy; Impairment; Incidence; Infant; Intervention Trial; Laboratory Personnel; Laboratory Technicians; Lead; Leadership; Life; Malnutrition; Mission; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Natural History; Nursing Research; Oral; Participant; Patients; Performance; Phenotype; Physicians; Population; Population Study; Prevalence; Prevention; Quality of life; Reaction; Recruitment Activity; Research; Research Assistant; Research Personnel; Sampling; Schedule; Scientist; Site; Team Nursing; Teleconferences; Telephone; Time; Training; Universities; Wood material; base; clinical investigation; cohort; desensitization; early onset; effective therapy; epigenomics; experience; high risk; high risk infant; innovation; meetings; member; metabolomics; next generation; novel strategies; oral immunotherapy; patient oriented; patient population; peer; performance site; placebo controlled study; prevent; research study; safety study; skin prick test

Abstract / Summary Peanut allergy is common, affecting 1-2% of children, and as opposed to most other childhood food allergies, usually persists lifelong. Even more concerning, for reasons that are not yet clear the prevalence of peanut allergy has increased 2-3 fold in the last 20 years. While the LEAP study convincingly demonstrated that peanut allergy could be prevented in about 80% of high risk infants by early peanut introduction, it is important to recognize that early peanut introduction is not universally successful in the prevention of peanut allergy. For example, 2% of the enrolled babies were already allergic, defined by a failed oral peanut challenge at study entry, and an additional 11% were assumed to be allergic based on a large peanut prick skin test and therefore excluded from the baseline challenge. This phenotype of babies with exceptionally early onset peanut allergy not only presents an unmet need from a clinical standpoint, since most will go on to have lifelong peanut allergy, they also provide a unique opportunity to study the underlying mechanisms for the development of food allergy. In this project, we will have the opportunity to characterize these infants from both a clinical and mechanistic standpoint, comparing them to their peers who have either no peanut sensitization or sensitization without allergy. Then, as our primary aim, we will study the safety and efficacy of peanut oral immunotherapy in this cohort, which to our knowledge will be the earliest initiation of any form of specific immunotherapy for the treatment of food allergy. We will accomplish this through the following specific aims: 1) To conduct a double- blind, placebo-controlled (DBPC) study of peanut OIT in 4 to 11 month old infants with peanut allergy. We hypothesize that treatment at this early age will be safe and effective, inducing not just a high rate of desensitization but also of sustained unresponsiveness (SU), far higher than has been demonstrated in older children and adolescents. 2) To characterize a cohort of infants with early onset peanut allergy, or deemed to be at high risk for the development of peanut allergy, who will be categorized for this study into three distinct subsets: those who are not peanut sensitized or allergic, those who are sensitized but not allergic, and those who have already developed clinical peanut allergy at the time of recruitment. 3) To collaborate with the investigators of the Biomarker Facility and Opportunity Fund to carefully select samples for more detailed mechanistic studies, potentially including metabolomics, microbiomics, epigenomics, and CyTOF, in addition to the usual biomarkers to be used in the immunologic profiling in Aim 1. We believe that the OIT trial will have a profound impact on the future treatment of peanut and other food allergies, and that this study will be highly informative in defining the clinical and immunologic factors that are most important in the development of peanut allergy.

摘要/概要 花生过敏很常见，影响1-2%的儿童，与大多数其他儿童食物过敏相反， 通常会持续终生。更令人担忧的是，由于尚不清楚的原因，花生的流行程度 在过去的20年里，过敏症增加了2-3倍。虽然LEAP研究令人信服地证明， 在大约80%的高危婴儿中，通过早期引入花生可以预防过敏，重要的是， 认识到早期引进花生在预防花生过敏方面并不普遍成功。为 例如，2%的登记婴儿已经过敏，定义为研究时口服花生挑战失败 根据大花生点刺皮肤测试，另外11%的人被假设为过敏，因此 从基线挑战中排除。这种花生过敏的婴儿表现出的表型 不仅从临床角度来看存在未满足的需求，因为大多数人将继续终身对花生过敏， 它们还提供了一个独特的机会来研究食物过敏发展的潜在机制。 在这个项目中，我们将有机会从临床和机制两个方面来描述这些婴儿的特征。 站在他们的立场上，将他们与那些没有花生敏感性或没有花生敏感性的同龄人进行比较， 过敏然后，作为我们的主要目标，我们将研究花生口服免疫疗法在这方面的安全性和有效性。 队列，据我们所知，这将是最早开始的任何形式的特异性免疫治疗， 食物过敏的治疗我们将通过以下具体目标来实现这一目标：1）进行双重- 在4至11个月大的花生过敏婴儿中进行的花生OIT的盲法、安慰剂对照（DBPC）研究。我们 假设在这么早的年龄进行治疗是安全有效的，不仅会导致高发病率， 脱敏，但也持续无反应（SU），远远高于已证明在老年人 儿童和青少年。2)描述早发性花生过敏或被认为 花生过敏的高风险发展，谁将被分为三个不同的研究 亚群：不对花生过敏或过敏的人，过敏但不过敏的人， 在招募时已经出现临床花生过敏的人。3)为了与 生物标志物设施和机会基金的研究人员仔细选择样本， 机制研究，可能包括代谢组学、微生物组学、表观基因组学和CyTOF， 目标1中免疫学分析中使用的常用生物标志物。我们认为，OIT审判将有一个 对未来治疗花生和其他食物过敏产生深远影响，并认为这项研究将是高度 在定义花生发育中最重要的临床和免疫因素方面提供了信息 过敏