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.
Eosinophilic Esophagitis (EoE) is an increasingly recognized rare allergic disease that affects both children and adults. EoE is characterized by symptoms such as vomiting, abdominal pain, trouble swallowing, and food impaction. In EoE, the esophageal lining develops an increased number of white blood cells called eosinophils. Eosinophils are white blood cells associated with other allergic diseases such as asthma and eczema. Evidence to date suggests that EoE affects children with a prevalence of ~1:10,000. If untreated, children and adults with EoE can develop esophageal narrowings that can lead to esophageal food impactions that may require emergency medical intervention. The cause of EoE and how these complications develop is uncertain. Currently, the only method to monitor the activity of this disease is to perform an endoscopy with biopsy, an invasive procedure that requires putting a flexible tube into the esophagus and taking a piece of tissue. Thus, a better understanding of the causes, and less invasive, inexpensive and better-tolerated tests are urgently needed to improve the lives of patients with EoE. This proposal seeks to address both these issues. The global objective of this project is therefore to bring a new device, the 'Esophageal String Test' (EST) to commercialization, so that it can be used by physicians to monitor treatment success (or failure) in children and adults with EoE. Here, we hypothesize that the EST captures a selective group of proteins or biomarkers that reflect disease activity. The Esophageal String Test (EST) is based on an old test that was originally used to make the diagnosis of an intestinal infection. This test consists of using a capsule that is filled with a nylon string; one end of the string is pulled out of the small capsule and this end is taped to the cheek. The capsule is then swallowed and the capsule dislodges the string as it goes into the esophagus and upper intestinal tract. After being in place for a few hours, the tape is removed and the string containing the liquid esophageal secretions is pulled out of the mouth. This liquid is removed and analyzed for the EoE biomarkers. Our recent publication showed that ESTs can capture proteins that are increased in patients with EoE after the EST is in the esophagus for 12-hours. In this project, we will use ESTs in a more clinically relevant 1-hour collection period to obtain esophageal samples that will: (1) establish a panel of specific proteins that are present in the esophagus of patients with EoE with active inflammation, and will call this the EoE Biomarker Panel (EBP), and (2) determine whether the EBP can be used to monitor how well the treatment is working. At least three Public Health Impacts should result from these studies: (1) ESTs may be used as safe, inexpensive, and minimally invasive tools to monitor esophageal inflammation in EoE during treatment instead of using endoscopy with biopsy; (2) ESTs may allow the identification of biomarkers relevant to disease progression and treatment responses in EoE; and (3) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.
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