Tolerance induction through non-avoidance to prevent persistent food allergy

通过非回避诱导耐受，以预防持续性食物过敏

• 批准号: 428057545
• 负责人: Professorin Dr. Kirsten Beyer
• 金额: --
• 依托单位: Klinik für Dermatologie, Venerologie und Allergologie (CCM)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/428057545?language=en
• 关键词: Tolerance; induction; through; non; avoidance

Patients with peanut (PN) and tree nut (TN) allergy rarely outgrow their disease. The reason might be that patients maintain a strict elimination diet independent of their eliciting dose (ED). Therefore, we started in the 1st funding period a randomized placebo controlled trial (RCT) in patients with PN- or TN-allergy and ED ≥ 300 mg protein. We hypothesized that regularly consumption below the ED is safe and will result in clinical tolerance or an ED increase within one year compared to patients on complete avoidance. In parallel, we performed an observational study (OS) on sensitized but tolerant patients with the hypothesis that regular allergen consumption prevents the re-development of food allergy (FA).Despite major restrictions due to the COVID 19 pandemic, 139 patients (84 children and 55 adults) completed the screening double blind, placebo-controlled food challenge. 72 patients reacted at ≥ 300 mg protein and were included in the RCT with 34 patients randomized to the avoidance and 38 patients to the liberal diet group. 28 patients were tolerant and entered the OS. We observed major differences in the symptom profile of pediatric and adult patients and analyzed this further in existing data. Our data showed that cardiovascular symptoms are often occurring in adults but rarely in children. Furthermore, adults suffer from a higher impairment of the FA-specific quality of life than children. So far 28 patients completed the RCT. The group with the liberated diet showed a significant increase in the ED, which was not observed in the allergen avoidance group. No serious adverse events due to allergen consumption have been reported. In the OC, 10 patients completed the 1-year assessment. All patients consumed the allergen frequently.We will apply for a cost-neutral prolongation of 1 year in order to finalize the recruitment and follow-up of the RCT and the OC. In parallel we will follow-up the recruited patients for another year in the 2nd funding period. Allergic patients with a liberated diet will continue this diet for another year with a further increase of the allergen amounts in order to assess long-term efficacy and safety. Patients from the strict allergen avoidance group will cross-over to the consumption group allowing the direct comparison of strict allergen avoidance versus a liberated diet within the same patient. All patients who became clinically tolerant will enter the OS.Our data will show whether a liberated diet is safe and promotes oral tolerance development in patients with established FA. The obtained bio samples (serum, PBMCs, saliva, stool and skin swaps) will support the mechanistic projects within this clinical research unit to better characterize and predict FA and tolerance.

患有花生（PN）和树坚果（TN）过敏的患者很少会长大。原因可能是患者保持严格的排除饮食，而不受其诱发剂量（艾德）的影响。因此，我们在第一个资助期开始了一项在PN或TN过敏且艾德≥ 300 mg蛋白质的患者中进行的随机安慰剂对照试验（RCT）。我们假设，定期消费低于艾德是安全的，并会导致临床耐受性或艾德增加一年内相比，患者完全避免。与此同时，我们对致敏但耐受的患者进行了一项观察性研究（OS），假设定期食用过敏原可以防止食物过敏（FA）的再次发生。尽管由于COVID 19大流行而受到重大限制，但仍有139名患者（84名儿童和55名成人）完成了筛选双盲，安慰剂对照的食物挑战。72例患者在≥ 300 mg蛋白质时发生反应，并被纳入RCT，其中34例患者被随机分配至避免饮食组，38例患者被随机分配至自由饮食组。28例患者耐受并进入OS。我们观察到儿童和成人患者症状特征的主要差异，并在现有数据中进一步分析。我们的数据显示，心血管症状经常发生在成人中，但很少发生在儿童中。此外，成年人比儿童遭受更高的FA特异性生活质量的损害。到目前为止，有28名患者完成了RCT。自由饮食组显示出艾德的显著增加，而在过敏原避免组中未观察到。尚未报告过敏原摄入导致的严重不良事件。在OC中，10例患者完成了1年评估。所有患者均经常使用过敏原，我们将申请延长1年的费用中立，以完成RCT和OC的招募和随访。同时，我们将在第二个资助期对招募的患者进行为期一年的随访。具有自由饮食的过敏患者将继续这种饮食一年，进一步增加过敏原的量，以评估长期疗效和安全性。来自严格过敏原避免组的患者将交叉到消费组，从而允许在同一患者中直接比较严格过敏原避免与自由饮食。所有临床耐受的患者都将进入OS。我们的数据将显示自由饮食是否安全，并促进已确定FA患者的口服耐受性发展。获得的生物样本（血清、PBMC、唾液、粪便和皮肤交换物）将支持该临床研究单位内的机制项目，以更好地表征和预测FA和耐受性。