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: 8423687
• 负责人: Brian Vickery
• 金额: $ 12.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8423687
• 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 Intervention; 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. 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）：该K23奖申请描述了Brian Vickery博士的职业发展计划，Brian Vickery博士是杜克大学医学中心小儿过敏和免疫学的讲师。该奖项将为Vickery博士提供必要的支持和培训，以发展为专门研究儿童过敏疾病的独立医师评估者。具体而言，该奖项将使维克里博士能够实现以下目标：（1）掌握设计和执行临床试验所需的技能； （2）熟练精通高级生物统计技能，适合分析纵向研究； （3）开发机械免疫监测测定方面的专业知识； （4）实现独立的研究职业，从事高影响力的患者研究研究，重点是基于免疫耐受性的过敏性疾病疗法。为了实现这些目标，Vickery博士召集了一个由食品过敏和免疫耐受性的国际专家韦斯利·伯克斯（Wesley Burks）领导的指导咨询委员会。 Burks博士将领导其他具有丰富指导经验的著名调查员团队，其科学利益共同包括基本和转化免疫学，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，药理学和高级实验室方法的高级教学课程来补充这一密集的职业发展指导。花生过敏是严重且可能致命的免疫问题，影响了美国和其他发达国家约1％的儿童。没有有效的疾病调整疗法，患者的身体和心理发病率很高，包括生命质量的大幅降低，这是由于最近的研究强调了过敏性反应的潜在可塑性，这是由于永远存在威胁生命过敏反应的风险而导致的。生命以及在这个关键时期口服暴露的作用，我们设计了一项单中心随机临床试验，以测试40名新诊断的花生过敏儿童的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：产生一种新的治疗方法，可以通过瞬时改变反应性并降低治疗中的过敏反应（即脱敏）来迅速受益于花生过敏受试者（AIM I）；评估这种治疗方法随着时间的推移永久改变花生特异性免疫反应的能力，从而允许停用治疗（即耐受性）（AIM I）；并了解其作用机理（AIM II）。在提供临床研究方面的指导培训经验的同时，这项创新的试验直接着重于几个重要的知识差距，必须解决，以开发首个临床上可用的食物过敏治疗并改变护理标准。这项工作的结果有可能通过开发一种安全，廉价，可行且有效的改良疾病疗法来改变花生过敏的方式，并可以立即为婴儿和幼儿提供。该项目将研究幼儿花生口服免疫疗法的早期干预，对人类免疫耐受性产生重要的新科学知识，并研究治疗对与健康相关的生活质量的影响。