SEAL (Stopping Atopic dermatitis and ALlergy) Study: Prevent allergy by enhancing the skin barrier

SEAL（阻止特应性皮炎和过敏）研究：通过增强皮肤屏障预防过敏

• 批准号: 10448393
• 负责人: HELEN A BROUGH
• 金额: $ 173.84万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-14 至 2023-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448393
• 关键词: 1 year old; 3 year old; Allergens; Allergic inflammation; Allergy to peanuts; Anti-Inflammatory Agents; Atopic Dermatitis; B-Lymphocytes; Basophils; Biological Markers; Blood; CD8B1 gene; Caring; Cells; Child; Clinical; Clinical Research; Complex; Country; Cream; Cytometry; Development; Disease; Eczema; Emollients; Epidemic; Epithelial; Food Hypersensitivity; Functional disorder; Genes; Gold; Hypersensitivity; IgE; Immune response; Immunoglobulin Class Switching; Incidence; Infant; Inflammation; Inhalant dose form; Interleukin-10; Interleukin-13; Intervention; Intervention Trial; Learning; Life; Lipids; Lymphoid Cell; Mediating; Metagenomics; Monitor; Oatmeal Powder; Oral; Participant; Patients; Play; Prevalence; Prevention; Proteins; Proteomics; Randomized; Regulatory T-Lymphocyte; Research; Risk; Role; Secondary Prevention; Severities; Skin; Skin Care; Somatic Mutation; Staphylococcus aureus; Steroids; Stratum corneum; T cell receptor repertoire sequencing; TSLP gene; Techniques; Testing; Th2 Cells; Time; Topical application; Variant; allergic response; arm; atopy; cohort; commensal bacteria; dysbiosis; filaggrin; food allergen; food challenge; food consumption; genetic testing; high risk infant; immune function; improved; infancy; mast cell; microbial; monocyte; novel; oral tolerance; prevent; primary endpoint; prospective; recruit; repaired; respiratory; seal; secondary outcome; skin barrier; skin microbiota; standard of care; transcriptomics; treatment arm; treatment group; trial design; γδ T cells

Project Summary and Abstract for the SEAL (Stopping Eczema and ALlergy) Study Food allergy (FA) is an epidemic among children in the U.S., U.K., and other countries. There is increasing evidence that epicutaneous allergen sensitization through a dysfunctional skin barrier results in allergic responses whereas early consumption of food allergens induces oral tolerance, as described by the dual allergen exposure hypothesis. In the Learning Early About Peanut LEAP and Enquiring About Tolerance (EAT) studies, dry skin and the severity and the duration of eczema or atopic dermatitis (AD) in the 1st year of life were predictors of peanut allergy (PA) and sensitization. In the SEAL study, we aim to intervene very early in a high-risk infant group, as soon they have the earliest onset of dry skin or eczema in the 1st 10 weeks of life, but before they have developed allergies. By reducing the duration and severity of eczema and preventing eczema exacerbations, we aim to prevent epicutaneous allergen sensitization and significantly reduce the incidence of FA. Our primary objective is to test if the combination of trilipid skin emollient use early in life with proactive topical steroids decreases the prevalence of FA compared to controls. We propose a randomized (1:1), controlled trial design for infants with dry skin or eczema (n=750 total) to compare the effect of proactive treatment against a reactive treatment group for the prevention of FA, by reducing dry skin, and the severity and duration of eczema in early infancy. We will test our hypothesis with the following specific aims using world-class clinical research units known for excellent recruitment and retention of patient cohorts, mechanistic testing, and state of the art research. Specific Aim 1: To determine if proactive versus reactive treatment will reduce the occurrence of FA in a prospective, randomized, and controlled intervention trial of infants with eczema. Specific Aim 2: To test whether the skin of children in the proactive treatment will show improved epithelial barrier markers with increased commensal bacteria colonization. Specific Aim 3: To determine whether proactive treatment will be associated with protective immune responses. If the aims are achieved, our proposal will make a clinical impact by providing a new, clinical strategy to prevent the occurrence of FA in young infants that present with the earliest signs of dry skin or eczema.

密封的项目摘要和摘要（停止湿疹和过敏）研究 食物过敏（FA）是美国，英国和其他国家的儿童的流行病。有在增加 表明通过功能失调的皮肤屏障敏化的表皮过敏原敏化导致过敏性 反应，而食物过敏原的早期消费诱导口服耐受性，如双重所述 过敏原暴露假设。在早期学习花生飞跃和询问宽容（EAT） 研究，皮肤干燥以及生命第一年的湿疹或特应性皮炎（AD）的严重程度和持续时间 是花生过敏（PA）和敏化的预测因子。在密封研究中，我们的目标是在很早的早期进行干预 高风险的婴儿组，他们在生命的第1周就有最早的皮肤干或湿疹发作 但是在他们发展过敏之前。通过减少湿疹的持续时间和严重程度并防止 湿疹加剧，我们旨在防止表皮过敏原敏化，并显着降低 FA的发病率。我们的主要目的是测试生命早期三脂皮肤润肤剂的结合与 与对照组相比，主动局部类固醇可降低FA的患病率。 我们为患有干燥皮肤或湿疹的婴儿（总计n = 750）的随机（1：1），对照试验设计 比较主动治疗与反应性治疗组预防FA的影响， 减少皮肤干燥，以及婴儿早期湿疹的严重程度和持续时间。我们将通过 遵循特定目标，使用以优秀招聘和保留的世界一流临床研究单位 患者队列，机械测试和最先进的研究状态。特定目标1：确定是否主动 与反应性治疗相对于反应性治疗将减少前瞻性，随机和控制的FA的发生 湿疹婴儿的干预试验。特定目的2：测试儿童的皮肤是否积极主动 治疗将显示出增强的上皮屏障标记，并增加共生细菌定殖。 特定目的3：确定主动治疗是否与保护性免疫有关 回答。如果实现了目标，我们的建议将通过提供新的临床，从而产生临床影响 防止在皮肤干燥或最早出现的年轻婴儿中发生FA的策略 湿疹。