An allergen-specific immune signature-directed diet vs sham diet for treatment of eosinophilic esophagitis: A pilot-feasibility study

过敏原特异性免疫特征导向饮食与假饮食治疗嗜酸性粒细胞性食管炎：一项试点可行性研究

• 批准号: 10612916
• 负责人: Evan Samuel Dellon
• 金额: $ 31.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-30 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612916
• 关键词: Acceleration; Address; Adherence; Aftercare; Algorithms; Allergens; Biological Assay; Biological Markers; Biopsy; Blood; CD4 Positive T Lymphocytes; Chronic Disease; Clinical; Clinical Trials; Consumption; Control Groups; Data; Deglutition; Deglutition Disorders; Diet; Diet Monitoring; Diet therapy; Digestive System Disorders; Disease; Endoscopy; Eosinophilic Esophagitis; Esophageal Stenosis; Esophageal mucous membrane; Esophagus; Feasibility Studies; Food; Food Hypersensitivity; Foundations; Future; Goals; Histologic; Hypersensitivity; IgG4; Immune; Incidence; Infiltration; Knowledge; Measures; Mediating; Monitor; Morbidity - disease rate; NIH Program Announcements; Outcome; Pathology; Patients; Pharmaceutical Preparations; Placebo Control; Prevalence; Process; Reproducibility; Research; Research Project Grants; Risk; Serum; Skin; Symptoms; Techniques; Testing; Time; Translational Research; United States National Institutes of Health; blood-based biomarker; design; dietary; eosinophil; eosinophil peroxidase; eosinophilic inflammation; feasibility testing; feasibility trial; gastrointestinal; individual patient; innovation; multidisciplinary; novel; peripheral blood; procedure cost; randomized, clinical trials; response; treatment response

An allergen-specific immune signature-directed diet vs sham diet for treatment of eosinophilic esophagitis: A pilot-feasibility study ABSTRACT Eosinophilic esophagitis (EoE) is a chronic disease defined by abnormal infiltration of eosinophils into the esophageal mucosa, leading to dysphagia, progressive esophageal stenosis, and food impaction. The incidence and prevalence are rising dramatically, and EoE is now a major cause of upper gastrointestinal morbidity. Because EoE is allergen-mediated and triggered by foods, dietary elimination is the primary non- pharmacologic treatment. However, the approach to dietary elimination is sub-optimal, burdensome, and time- consuming. Currently available blood- or skin-based allergy tests do not reliably identify food triggers of EoE, so multiple foods must be empirically removed from the diet. Adherence to these restrictive diets is difficult, the same approach is used for all patients, and foods that are not eliminated may still be triggers. Multiple endoscopies are required to identify triggers, and these invasive and costly procedures carry risks. Two major issues must be addressed to allow widespread application of dietary therapy in EoE. First, if accurate allergy tests were available, treatment could be personalized and streamlined. Foods likely to be triggers in an individual patient could be eliminated, and foods unlikely to provoke eosinophilic inflammation could be retained. Second, if non-invasive biomarkers were available to monitor treatment response, the need for endoscopies could be greatly reduced. To begin to address these two major knowledge gaps, we developed a novel allergen-specific immune signature to guide dietary elimination. This technique predicts food triggers based on food-specific IgG4 levels in esophageal biopsies and CD4+ T-cell stimulation assays in peripheral blood. In initial testing, this approach was more accurate than traditional skin-based allergy tests. We have also identified a promising biomarker, eosinophil peroxidase (EPX), that can be measured in the serum and tracks with treatment response as measured on esophageal biopsies. The proposed study has been designed to be highly responsive to PAS 20-160, a new “small R01” mechanism that encourages pilot/feasibility clinical trials that lay the foundation for larger trials. To generate key data to estimate effect sizes, we will conduct a pilot randomized clinical trial of the allergen-specific immune signature-directed diet elimination vs sham diet elimination with the following specific aims: 1) To estimate the effect of allergen-specific immune signature- directed dietary elimination compared to sham elimination on esophageal eosinophil counts and symptoms of dysphagia in patients with EoE; and 2) To assess serum EPX as a non-invasive biomarker and estimate effect sizes for monitoring dietary elimination treatment response in patients with EoE. This innovative pilot/feasibly trial will be conducted by an existing multidisciplinary team with recognized expertise in EoE, clinical trials, food allergy, pathology, and translational science. It will ultimately lead to a major clinical impact on the treatment and monitoring of EoE by individualizing dietary elimination and streamlining monitoring of dietary elimination using non-invasive biomarkers, so patients can avoid the time, effort, and risk of empiric dietary elimination.

过敏原特异性免疫特征导向饮食与假饮食治疗嗜酸性粒细胞性白细胞增多症的比较 食管炎：可行性初步研究 摘要 嗜酸性粒细胞性食管炎（EoE）是一种慢性疾病，其特征是嗜酸性粒细胞异常浸润到食管组织中， 食管粘膜，导致吞咽困难、进行性食管狭窄和食物嵌塞。的 EoE的发病率和患病率急剧上升，现在是上消化道疾病的主要原因， 发病率由于EoE是由过敏原介导的，并由食物引发，饮食消除是主要的非过敏原。 药物治疗然而，饮食消除的方法是次优的，繁重的，和时间- 消耗。目前可用的基于血液或皮肤的过敏测试不能可靠地识别EoE的食物触发因素， 因此必须根据经验从饮食中去除多种食物。坚持这些限制性饮食是困难的， 对所有病人都采用同样的方法，没有被消除的食物仍然可能是诱因。多 需要内窥镜检查来识别触发器，这些侵入性和昂贵的程序具有风险。两大 必须解决的问题，使饮食疗法在EoE的广泛应用。首先，如果准确过敏 如果可以进行测试，治疗可以个性化和简化。食物可能是触发在一个 可以排除个别患者，不太可能引起嗜酸性炎症食物可以 保留。其次，如果非侵入性生物标志物可用于监测治疗反应， 内窥镜检查可以大大减少。为了开始解决这两个主要的知识差距，我们开发了一个 新的过敏原特异性免疫特征，以指导饮食消除。这项技术可以预测食物触发 基于食管活检中的食物特异性IgG 4水平和外周血中的CD 4 + T细胞刺激测定， 血在最初的测试中，这种方法比传统的皮肤过敏测试更准确。我们有 还确定了一种有前途的生物标志物，嗜酸性粒细胞过氧化物酶（EPX），可以在血清中测量， 跟踪食管活检测量的治疗反应。这项研究的目的是 高度响应PAS 20-160，这是一种新的“小R 01”机制，鼓励试点/可行性临床 这些试验为更大规模的试验奠定了基础。为了生成估计效应量的关键数据，我们将进行 过敏原特异性免疫信号导向的饮食消除与假饮食的初步随机临床试验 消除具有以下特定目的：1）评估过敏原特异性免疫特征的作用- 与假消除相比，直接饮食消除对食管嗜酸性粒细胞计数和 EoE患者的吞咽困难;和2）评估血清EPX作为非侵入性生物标志物并估计效果 用于监测EoE患者的饮食消除治疗反应。这一创新试点/可行 试验将由一个现有的多学科团队进行，该团队在EoE、临床试验、食品 变态反应病理学和转化科学它最终将导致对治疗的重大临床影响 通过个体化饮食消除和简化饮食消除监测来监测EoE 使用非侵入性生物标志物，因此患者可以避免经验性饮食消除的时间、精力和风险。