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: 10239246
• 负责人: HELEN A BROUGH
• 金额: $ 174.43万
• 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 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10239246
• 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.

SEAL（阻止湿疹和过敏）研究的项目摘要和摘要 食物过敏 (FA) 是美国、英国和其他国家儿童中的一种流行病。有越来越多 有证据表明，表皮过敏原通过功能失调的皮肤屏障致敏会导致过敏 反应，而早期食用食物过敏原会诱导口服耐受，正如双重描述所描述的 过敏原暴露假说。早期学习花生 LEAP 并探究耐受性 (EAT) 研究显示，皮肤干燥与出生后第一年湿疹或特应性皮炎 (AD) 的严重程度和持续时间有关 是花生过敏（PA）和致敏的预测因子。在海豹突击队的研究中，我们的目标是尽早干预 高危婴儿组，在出生后 10 周内最早出现皮肤干燥或湿疹， 但在他们出现过敏之前。通过减少湿疹的持续时间和严重程度并预防 湿疹恶化，我们的目标是预防表皮过敏原致敏并显着减少 FA 的发生率。我们的主要目标是测试在生命早期使用三脂类皮肤润肤剂是否与 与对照组相比，主动外用类固醇可降低 FA 的患病率。 我们针对皮肤干燥或湿疹的婴儿（总共 n=750）提出一项随机 (1:1) 对照试验设计，以 比较主动治疗组与反应性治疗组预防 FA 的效果，通过 减少婴儿早期皮肤干燥、湿疹的严重程度和持续时间。我们将用以下方法检验我们的假设 使用以出色的招募和保留而闻名的世界一流的临床研究单位来遵循特定目标 患者队列、机械测试和最先进的研究。具体目标 1：确定是否主动 在一项前瞻性、随机和对照研究中，与反应性治疗相比，将减少 FA 的发生 湿疹婴儿的干预试验。具体目标2：测试儿童皮肤是否处于主动状态 治疗将显示出上皮屏障标记物的改善以及共生细菌定植的增加。 具体目标 3：确定主动治疗是否与保护性免疫相关 回应。如果目标实现，我们的建议将通过提供新的临床方法来产生临床影响 预防最早出现皮肤干燥迹象或出现 FA 的策略 湿疹。