Phase 2 Study of Esophageal String Test in Diagnosing Eosinophilic Esophagitis

项目总结 嗜酸性食管炎(EoE)是一种少见的少见疾病，以儿童和成人为特征 出现恶心、呕吐、腹痛、吞咽困难和食物嵌塞等症状 伴有食道嗜酸性粒细胞增多症。到目前为止，唯一进行EoE诊断并遵循 对EoE的治疗反应是侵入性内窥镜检查和活检。虽然内窥镜检查通常是安全的，但 迫切需要准确、侵入性小、成本低、全面和持久的检测来确定 治疗效果。为了满足这一需求，我们将使用现有技术的一种新应用，即 Enterotest“(一种用于检测肠道贾第鞭毛虫病的基于字符串的测试)，用于测量食道炎症 (这里称为食管串试验-EST)。我们最近的出版物为 EST捕获患者管腔标本中食管炎性介质(生物标记物)的能力 受EoE影响，这些生物标记物与组织中发现的那些相关。我们新奇的初步数据 支持在1小时内采样EoE相关炎症蛋白生物标记物的理论基础和可行性 收集时间点。这些发现为使用EST作为新的微创技术提供了有力的支持 监测EOE疗效的仪器。因此，该项目全球目标是带来 将“食管串试验”(EST)推向商业化，使其可用于监测治疗 对患有EoE的儿童和成人的疗效。我们假设EST将捕获EoE生物标记物 反映疾病活动的面板(EBP)。具体目标是：(1)确定EoE生物标记小组 (EBP)，这将提高EST监测疾病活动的敏感性和特异性，以及(2)验证 EST EBP在1小时采样时间内监测治疗效果的能力。我们的支持性出版物 初步数据表明，在患有EoE的儿童和成人中使用EST是可行的 在通宵(12小时)测试中测量疾病活动(食管炎)，并缩短时间段， 目前在预定的内窥镜检查和活检之前进行。在这个项目中，我们建议缩短这一时间 1小时的测试，一个临床相关的时间点，将显著促进其使用和潜在的影响 门诊部设置。 公共卫生相关性/影响：这些研究应至少产生四个主要影响： (1)确定EBP将允许监测EoE中的食管炎症；(2)EBP将 与EoE的疾病进展、治疗反应、管理和发病机制有关，(3) EST EBP的验证将使快速和廉价的分析方法的开发成为可能，以用于后续治疗 反应，从而减少了目前进行活检的后续内窥镜检查的数量，以及 (4)在无法进行内窥镜检查和活检的情况下，提供监测EoE疾病活动的设备或 价格实惠。

PROJECT SUMMARY Eosinophilic esophagitis (EoE) is an increasingly recognized rare disease of children and adults characterized by symptoms including nausea, vomiting, abdominal pain, dysphagia and food impaction that occur in conjunction with esophageal eosinophilia. To date, the only method to make EoE diagnoses and follow treatment responses in EoE is invasive endoscopy with biopsy. While endoscopy is generally safe, an accurate, less invasive, inexpensive, comprehensive and durable test is urgently needed to determine therapeutic efficacy. To address this need, we will use a novel application of an existing technology, the Enterotest" (a string-based test used to detect intestinal Giardiasis), to measure esophageal inflammation (herein termed the Esophageal String Test - EST). Our recent publication provides proof-of-principle for the ability of ESTs to capture esophageal inflammatory mediators (biomarkers) in luminal samples from patients affected with EoE, and that these biomarkers correlate with those found in tissue. Our novel Preliminary Data support the rationale and feasibility of sampling EoE-associated inflammatory protein biomarkers in a 1-hour collection time point. These findings provide strong support for using ESTs as novel minimally invasive instruments to monitor therapeutic efficacy in EoE. The global objective of this project is therefore to bring the "Esophageal String Test" (EST) to commercialization, so that it can be used to monitor therapeutic efficacy in children and adults with EoE. We hypothesize that ESTs will capture an EoE Biomarker Panel (EBP) reflective of disease activity. The Specific Aims are to: (1) Identify an EoE Biomarker Panel (EBP) that will improve the sensitivity and specificity of the EST for monitoring disease activity, and (2) Validate the ability of the EST EBP to monitor therapeutic efficacy in a 1-hour sampling time. Our supportive published and Preliminary Data demonstrate the feasibility of using ESTs in both children and adults with EoE to measure disease activity (esophageal inflammation) in an overnight (12-hour) test, and shorter time periods, currently performed before a scheduled endoscopy with biopsy. In this project, we propose to shorten this time frame to a 1-hour test, a clinically relevant time point that will markedly facilitate its use and potential impact in the outpatient clinic setting. Public Health Relevance/Impacts: At least four major impacts should result from these studies: (1) Identification of an EBP will permit monitoring of esophageal inflammation in EoE; (2) the EBP will be relevant to following disease progression, treatment responses, management and pathogenesis of EoE, (3) validation of the EST EBP will enable development of rapid and inexpensive assays to follow treatment responses, thus reducing the number of follow-up endoscopies with biopsy that are currently performed, and (4) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.