ORAL IMMUNOTHERAPY FOR COW'S MILK ALLERGY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：牛乳过敏(CMA)是婴幼儿最常见的食物过敏，影响2-3%的总人口。目前对牛奶过敏的管理是避免所有形式的牛奶，直到身体自然产生耐受性。尽管以前的前瞻性研究显示出良好的预后，高达85%的儿童在3岁前就不会过敏了，但我们看到越来越多的儿童的CMA持续到学龄及以后。对于这些孩子来说，避免喝牛奶的另一种选择将是理想的，因为牛奶本身就有风险。 原理：皮下免疫疗法(“过敏针”)用于治疗环境过敏症的记录由来已久。看来，这种针对食物的免疫疗法的副作用高得令人无法接受。使用口服免疫疗法治疗食物过敏的初步研究似乎更安全，也可能有效。 研究问题：牛奶过敏的口服免疫疗法在降低或消除牛奶过敏患者对牛奶蛋白的敏感性方面是否安全有效？ 设计：这是一项前瞻性、多中心、临床试验，涉及6至21岁患有持续性牛奶过敏的儿童。这些儿童将在两个地点(约翰霍普金斯大学和杜克大学)招募，并将接受初步筛查和双盲、安慰剂对照的食物挑战(DBPCFC)，以确定对牛奶的反应阈值剂量。患者将接受22-30周的牛奶口服免疫疗法(OIT)或安慰剂治疗。那些达到足够的OIT维持量的人将接受第二次DBPCFC。那些出现脱敏症的人将继续每天摄入牛奶，并接受第三次DBPCFC。治疗组中未脱敏的患者将恢复严格回避。安慰剂组的患者将被提供开始治疗或继续严格避免牛奶。最初将定期收集症状和饮食信息。血液检查、皮肤点刺试验(SPTS)和肺功能试验(PFT)将在最初和定期进行。 研究人群：6岁至21岁的儿童，有牛奶症状过敏史，牛奶血液或皮肤测试呈阳性，将被考虑参加。 结果衡量标准： 主要剂量：治疗后能耐受初始OFC阈值剂量的四倍或最大OFC剂量8克的患者的百分比。 次要： O研究期间按方案定义的严重过敏反应的发生率 O研究期间所有严重不良事件的发生率 O所有不良事件的发生率 O评估牛奶-IgE、m-IgG4和总IgE在OIT期间和牛奶过敏持续或缓解期间的任何变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2-3% of the general population. The current management of milk allergy is to avoid all forms of milk until the body naturally develops tolerance. Although previous prospective studies show a good prognosis, with up to 85% of children outgrowing their allergy by age 3, we see an increasing number of children whose CMA persists into school age and beyond. For these children, an alternative to milk avoidance, which carries it's own risks, would be ideal. RATIONALE: Subcutaneous immunotherapy ("allergy shots") has a long record of use for treatment of environmental allergies. It appears that this type of immunotherapy for foods has an unacceptably high rate of side effects. Initial studies using orally administered immunotherapy for food allergies appears safer and potentially effective. STUDY QUESTION: Can oral immunotherapy for milk allergy be safe and effective in reducing or eliminating sensitivity to cow's milk protein in milk-allergic individuals? DESIGN: This is a prospective, multi-center, clinical trial involving children aged 6 to 21 years with persistent cow's milk allergy. These children will be recruited at 2 sites (Johns Hopkins and Duke University) and will undergo initial screening and double-blind, placebo-controlled, food challenge (DBPCFC) to confirm threshold dose for reactivity to milk. Patients will be treated with milk oral immunotherapy (OIT) or placebo for 22-30 weeks. Those who reach an adequate maintenance dose for OIT will undergo a second DBPCFC. Those who develop desensitization will continue with daily milk intake and undergo a third DBPCFC. Those in the treatment group who are not desensitized will return to strict avoidance. Those in placebo group will be offered to begin treatment or continue with strict milk avoidance. Symptom and diet information will be collected initially and at regular intervals. Blood-work, skin prick tests (SPTs), and pulmonary function tests (PFTs), will be done initially and at periodic intervals. STUDY POPULATION: Children between the ages of 6 and 21 years with a history of symptomatic allergy to milk and a positive blood or skin test to milk will be considered for enrollment. OUTCOME MEASURES: Primary: The percentage of patients who can tolerate four times the initial OFC threshold dose or the maximum OFC dose of 8 grams after therapy. Secondary: o Incidence of protocol-defined severe hypersensitivity reactions during the study o Incidence of all serious adverse events during the study o Incidence of all adverse events o To assess for any changes in milk-IgE, m-IgG4, and total IgE during OIT and as milk allergy persists or resolves.