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: 10413334
• 负责人: Evan Samuel Dellon
• 金额: $ 31.53万
• 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/10413334
• 关键词: 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; Lead; Measures; Mediating; Monitor; Morbidity - disease rate; NIH Program Announcements; Outcome; Pathology; Patients; Pharmaceutical Preparations; Placebos; Prevalence; Process; Randomized Clinical Trials; Reproducibility; Research; Research Project Grants; Risk; Serum; Skin; Symptoms; Techniques; Testing; Time; Translational Research; United States National Institutes of Health; base; blood-based biomarker; design; dietary; eosinophil; eosinophil peroxidase; eosinophilic inflammation; feasibility testing; gastrointestinal; individual patient; innovation; multidisciplinary; novel; peripheral blood; procedure cost; 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定向饮食与假饮食治疗嗜酸性粒细胞增多症的比较 食管炎：一项试点可行性研究 抽象的 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中。 食管粘膜，导致吞咽困难、进行性食管狭窄和食物嵌塞。 发病率和患病率急剧上升，EoE 现在是上消化道疾病的主要原因 由于 EoE 是由过敏原介导并由食物引发的，因此饮食消除是主要的非致病因素。 然而，通过饮食消除的方法不是最理想的、繁琐的且耗时的。 目前可用的基于血液或皮肤的过敏测试无法可靠地识别 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很困难的， 对所有患者均采用相同的方法，未消除的食物仍可能是诱因。 需要进行内窥镜检查来确定触发因素，这些侵入性且昂贵的手术存在两个主要风险。 要让饮食疗法在 EoE 中广泛应用，必须解决的问题首先是是否准确的过敏。 可以进行测试，可以进行个性化和简化的治疗 食物可能会引发这种情况。 可以消除个别患者，并且可以使用不太可能引起嗜酸性粒细胞炎症的食物 其次，如果可以使用非侵入性生物标志物来监测治疗反应，则需要 为了开始解决这两个主要的知识差距，我们开发了一种内窥镜检查方法。 新颖的过敏原特异性免疫特征可指导饮食消除，该技术可预测食物触发因素。 基于食管活检中食物特异性 IgG4 水平和外周血中 CD4+ T 细胞检测刺激 在初步测试中，这种方法比传统的基于皮肤的过敏测试更准确。 还发现了一种有前途的生物标志物，即嗜酸性粒细胞过氧化物酶（EPX），可以在血清中进行测量，并且 该研究旨在跟踪食管活检测量的治疗反应。 对 PAS 20-160 高度敏感，这是一种新的“小 R01”机制，鼓励试点/可行性临床 为更大规模的试验奠定基础的试验为了生成估计效应大小的关键数据，我们将进行一项试验。 过敏原特异性免疫特征定向饮食消除与假饮食的试点随机临床试验 消除具有以下具体目标：1）评估过敏原特异性免疫特征的影响 - 直接饮食消除与假消除对食管嗜酸性粒细胞计数和症状的影响 EoE 患者吞咽困难；2) 评估血清 EPX 作为非侵入性生物标志物并评估效果 用于监测 EoE 患者饮食消除治疗反应的尺寸，这是一项创新的试点/可行。 试验将由现有的多学科团队进行，该团队在 EoE、临床试验、食品等领域具有公认的专业知识 过敏、病理学和转化科学最终将对治疗产生重大临床影响。 通过个体化膳食消除和简化膳食消除监测来监测 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。