Optimizing Tolerance Induction in Peanut Allergy: The DEVIL Study

优化花生过敏的耐受诱导：DEVIL 研究

• 批准号: 8280207
• 负责人: Brian Vickery
• 金额: $ 3.57万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280207
• 关键词: Academic Medical Centers; Address; Adult; Advisory Committees; Affect; Allergens; Allergic; Allergy to peanuts; Anaphylaxis; Award; B-Lymphocytes; Basic Science; Biological Assay; Biometry; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Complement; Developed Countries; Development Plans; Diet; Disease; Dose; Double-Blind Method; Early treatment; Effectiveness; Emergency Situation; Environment; Epitopes; Ethics; Extramural Activities; Faculty; Food Hypersensitivity; Funding; Goals; Guidelines; Human; Hypersensitivity; Immune Tolerance; Immune response; Immunologic Monitoring; Immunologics; Immunology; Individual; Infant; International; Knowledge; Laboratories; Lead; Leadership; Length; Life; Lymphocyte; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Morbidity - disease rate; Names; Newly Diagnosed; Oral; Outcome; Outpatients; Patient Selection; Patients; Peanuts - dietary; Pharmacology; Physicians; Physiological; Pilot Projects; Placebo Control; Population; Proteins; Quality of life; Randomized; Randomized Clinical Trials; Regulatory T-Lymphocyte; Research; Research Design; Research Institute; Research Methodology; Research Personnel; Research Training; Resources; Risk; Role; Safety; T-Lymphocyte; Testing; Time; Toddler; Training; Training Programs; Training Support; United States National Institutes of Health; Visit; Work; aged; allergic response; base; career; career development; critical period; desensitization; design; experience; health related quality of life; high risk; immunoregulation; improved; innovation; instructor; interest; member; operation; oral immunotherapy; patient oriented research; pediatric pharmacology; psychologic; response; skills; standard of care

DESCRIPTION (provided by applicant): This K23 award application describes a career development plan for Dr. Brian Vickery, an Instructor in the Division of Pediatric Allergy and Immunology at Duke University Medical Center. This award will provide Dr. Vickery with the necessary support and training to develop into an independent physician-investigator specializing in allergic disorders of childhood. Specifically, the award will enable Dr. Vickery to accomplish the following goals: (1) to master skills necessary to design and execute clinical trials; (2) to become proficient in advanced biostatistical skills suitable for analysis of longituinal studies; (3) to develop expertise in mechanistic immune monitoring assays; and (4) to achieve an independent research career conducting high-impact patient- oriented research focusing on immune tolerance-based therapies for allergic disorders. To accomplish these goals, Dr. Vickery has assembled a mentorship advisory committee led by Dr. Wesley Burks, an international expert in food allergy and immunological tolerance. Dr. Burks will lead a team of other renowned investigators with extensive mentorship experience, whose scientific interests collectively include basic and translational immunology, pediatric pharmacology, and clinical trials. Dr. Vickery will complement this intensive career development guidance with advanced didactic coursework in biostatistics, research design, pharmacology, and advanced laboratory methods. Peanut allergy is a severe and potentially fatal immunologic problem affecting approximately 1% of children in the U.S. and other developed nations. Without an effective disease-modifying therapy, patients suffer significant physical and psychological morbidity, including the profound reduction in quality of life that results from an ever-present risk of life-threatening anaphylaxis Based on recent studies highlighting the potential plasticity of allergic responses early in life, and the role of oral exposure during this critical period, we have designed a single-center randomized clinical trial to test early intervention with low-dose and high-dose peanut oral immunotherapy (OIT) in 40 newly diagnosed peanut-allergic children aged 9 - 36 months. The goals of this project are: to produce a new treatment that would rapidly benefit peanut-allergic subjects, by transiently altering reactivity and lowering the risk of anaphylaxis while on treatmen (i.e., desensitization) (Aim I); to assess the ability of this treatment to permanently alter the peanut-specific immune response over time, allowing discontinuation of therapy (i.e., tolerance) (Aim I); and to understand its mechanism of action (Aim II). While providing a mentored training experience in clinical research, this innovative trial focuses directly on several critical knowlede gaps that must be addressed in order to develop the first clinically available food allergy treatment and change the standard of care. PUBLIC HEALTH RELEVANCE: The outcome of this work has the potential to change the way peanut allergy is treated, by developing a safe, inexpensive, feasible, and effective disease-modifying therapy that could be made immediately available to infants and toddlers. This project will study early intervention with peanut oral immunotherapy in young children, generate important new scientific knowledge of immunologic tolerance in humans, and examine the impact of treatment on health-related quality of life.

描述（由申请人提供）：这份 K23 奖项申请描述了杜克大学医学中心儿科过敏和免疫学部门的讲师 Brian Vickery 博士的职业发展计划。该奖项将为维克里博士提供必要的支持和培训，以使其发展成为一名专门研究儿童过敏性疾病的独立医师研究员。具体来说，该奖项将使维克里博士能够 完成以下目标：（1）掌握设计和执行临床试验所需的技能； (2) 精通适合纵向研究分析的高级生物统计技能； (3) 发展机械免疫监测分析方面的专业知识； (4) 实现独立的研究生涯，开展高影响力的以患者为导向的研究，重点关注基于免疫耐受的过敏性疾病疗法。为了实现这些目标，维克里博士组建了一个指导咨询委员会，由食物过敏和免疫耐受方面的国际专家韦斯利·伯克斯博士领导。伯克斯博士将领导一个由其他具有丰富指导经验的知名研究人员组成的团队，他们的科学兴趣共同包括基础和转化免疫学、儿科药理学和临床试验。 Vickery 博士将通过生物统计学、研究设计、药理学和先进实验室方法方面的高级教学课程来补充这一密集的职业发展指导。 花生过敏是一种严重且可能致命的免疫问题，影响着美国和其他发达国家约 1% 的儿童。如果没有有效的疾病缓解疗法，患者会遭受严重的身体和心理疾病，包括因始终存在的危及生命的过敏反应风险而导致生活质量大幅下降基于最近的研究，强调过敏反应早期的潜在可塑性生活，以及口腔暴露在这个关键时期的作用，我们设计了一项单中心随机临床试验，以测试对 40 名新诊断的花生过敏儿童进行低剂量和高剂量花生口服免疫疗法 (OIT) 的早期干预9 - 36 个月。该项目的目标是：通过暂时改变反应性并降低治疗期间过敏反应的风险（即脱敏），产生一种能够迅速使花生过敏受试者受益的新疗法（目标 I）；评估这种治疗随着时间的推移永久改变花生特异性免疫反应的能力，从而允许停止治疗（即耐受）（目标 I）；并了解其作用机制（目标 II）。在提供临床研究指导培训经验的同时，这项创新试验直接关注几个必须解决的关键知识差距，以便开发第一个临床可用的食物过敏治疗方法并改变护理标准。 公共健康相关性：这项工作的结果有可能改变花生过敏的治疗方式，通过开发一种安全、廉价、可行和有效的疾病缓解疗法，可以立即提供给婴儿和幼儿。该项目将研究对幼儿进行花生口服免疫疗法的早期干预，产生有关人类免疫耐受的重要新科学知识，并研究治疗对健康相关生活质量的影响。