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: 10768462
• 负责人: GIDEON LACK
• 金额: $ 188.34万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 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/10768462
• 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; Dryness; Eczema; Emollients; Epidemic; Epithelium; Food Hypersensitivity; Functional disorder; Genes; 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; Prevalence; Prevention; Proteins; Proteomics; Randomized; Recommendation; 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; comparison control; dysbiosis; filaggrin; food allergen; food challenge; food consumption; genetic testing; high risk infant; immune function; improved; infancy; mast cell; microbial; monocyte; novel; oral tolerance; patient retention; prevent; primary endpoint; prospective; recruit; repaired; respiratory; 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流行病。有越来越多的 皮肤表面变应原通过皮肤屏障功能障碍致敏导致过敏的证据 反应，而早期食用食物过敏原诱导口服耐受性，如Dual所描述的 过敏原暴露假说。在早期学习花生飞跃和询问耐受性(EAT) 湿疹或特应性皮炎(AD)出生第一年的严重程度和持续时间与皮肤干燥的研究 是花生过敏(PA)和致敏的预测因子。在海豹突击队的研究中，我们的目标是很早就进行干预 高危婴幼儿组，在出生后10周内最早出现皮肤干燥或湿疹， 但在他们患上过敏之前。通过缩短湿疹的持续时间和严重程度，预防 湿疹加重，我们的目标是防止皮肤表面性过敏原过敏，并显著减少 FA的发病率。我们的主要目标是测试三磷脂皮肤润肤剂的组合是否在生命早期与 与对照组相比，主动局部应用类固醇可降低FA的患病率。 我们提出了一项随机(1：1)对照试验设计，用于患有干性皮肤或湿疹的婴儿(共750例)。 比较主动治疗和反应性治疗组预防FA的效果，通过 减少皮肤干燥，减轻婴儿早期湿疹的严重程度和持续时间。我们将使用 遵循特定目标，使用世界一流的临床研究单位，以出色的招聘和保留而闻名 患者队列、机械测试和最先进的研究。具体目标1：确定是否积极主动 与反应性治疗相比，前瞻性、随机性和可控性治疗将减少FA的发生 婴幼儿湿疹干预试验。具体目标二：测试儿童皮肤是否处于主动状态 随着共生细菌定植的增加，治疗将显示上皮屏障标志物的改善。 具体目标3：确定主动治疗是否与保护性免疫有关 回应。如果目标实现，我们的建议将通过提供一种新的、临床的 预防最早出现皮肤干燥或干燥症状的婴幼儿发生FA的策略 湿疹。