Phase 2 Study of Esophageal String Test in Diagnosing Eosinophilic Esophagitis

描述(由申请人提供)： 嗜酸性食管炎(EoE)是一种罕见的儿童和成人疾病，其特征是恶心、呕吐、腹痛、吞咽困难和食物阻塞，这些症状与食道嗜酸性粒细胞增多症同时发生。到目前为止，唯一能对EoE作出诊断和追踪治疗反应的方法是有创的内窥镜检查和活检。虽然内窥镜检查通常是安全的，但需要一种准确、侵入性较小、廉价、全面和耐用的测试来确定治疗效果。为了解决这一需求，研究人员建议使用现有技术的一种新应用，Enterotest？(用于检测肠道贾第虫病的一种基于字符串的测试)来测量食管炎(这里称为食管串测试或EST)。研究人员指出，初步数据为EST捕获受嗜酸性食管炎患者管腔样本中的食管炎介质的能力提供了原理证据，表明：(1)食道粘膜活检组织中嗜酸性粒细胞衍生颗粒蛋白的水平与EST捕获样本中的定量水平相关，即EST捕获的管腔分泌物中的水平与粘膜炎症相关，以及(2)这些嗜酸性炎症的管腔生物标志物与EoE疾病活动显著相关。根据调查人员的说法，这些 研究结果支持使用EST作为新的微创工具来监测嗜酸性食管炎的治疗效果。拟在660名儿童和成人中进行的第二阶段多中心研究的具体目标是：(1)确定一个嗜酸性食管炎生物标志物小组，该小组将提高EST监测疾病活动性的敏感性和特异性，以及()验证EST食管炎生物标志物小组在1小时采样时间内监测治疗效果的能力。研究人员表示，初步数据表明，在患有EoE的儿童和成人中使用EST来测量疾病活动性(食管炎)是可行的，在通宵(12小时)测试中，并且时间更短，目前在预定的内窥镜检查和活检之前进行。在这个项目中，研究人员建议将这一时间框架缩短为1小时的测试，这是一个临床上相关的时间点，据信有助于在门诊环境中使用潜在的影响。

DESCRIPTION (provided by applicant): Eosinophilic esophagitis (EoE) is a rare disease of children and adults characterized by symptoms such as nausea, vomiting, abdominal pain, dysphagia, and food impaction, that occur in conjunction with esophageal eosinophilia. To date, the only method to make the diagnosis 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 needed to determine therapeutic efficacy. To address this need, the investigator proposes the use of 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 or EST). The investigator states that preliminary data provide proof-of-principle for the ability of ESTs to capture esophageal inflammatory mediators in luminal samples from patients affected with eosinophilic esophagitis, demonstrating that: (1) levels of eosinophil-derived granule proteins in esophageal mucosal biopsies correlate with the levels quantitated in the EST-captured samples, i.e., levels in luminal secretions captured by the EST correlate with mucosal inflammation, and (2) these luminal biomarkers of eosinophilic inflammation significantly correlate with EoE disease activity. According to the investigator these findings support the use of ESTs as novel minimally invasive instruments to monitor therapeutic efficacy in eosinophilic esophagitis. The Specific Aims of the proposed Phase 2, multicenter study in 660 children and adults are to: (1) identify an eosinophilic esophagitis biomarker panel that will improve the sensitivity and specificity of the EST for monitoring disease activity, and () validate the ability of the EST esophagitis biomarker panel to monitor therapeutic efficacy in 1-hour sampling time. The investigator states that preliminary data demonstrate the feasibility of using the EST 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 investigators propose to shorten this time frame to a 1-hour test, a clinically relevant time point that is believed to facilitate use an potential impact in the outpatient clinic setting.