Eosinophilic esophagitis (EoE) is a rare allergic disease characterized by esophageal infiltration of eosinophils. This inflammatory infiltrate leads to dysphagia, impaction of food, and esophageal stricture. There is no FDA approved medication for EoE and the only available therapy to halt disease progression is utilizing restrictive diets or off label steroid preparations which are fraught with compliance issues and inconsistent dosing respectively. Thus, there is a critical need for FDA approved therapies in order to improve outcomes. Clinical trials to date have used a diverse number of clinical scoring symptoms, histologic evaluations and physician assessments. Due in part to the heterogeneity in clinical symptoms of affected children and adults, demonstrating improved symptom outcomes has been a major obstacle in early EoE trials. Having an objective measure of esophageal function in this patient population would improve clinical trial outcomes. Endoluminal Functional Lumen Imagaing Probe or EndoFLIP is a new technique that uses high-resolution impedance palimetry to determine the distensibility of hollow gastrointestinal organs including the esophagus. Our preliminary work has shown that in patients with active EoE, there is a significantly less distensible esophagus. We therefore seek to use EndoFLIP to provide critical data to inform the design of future interventional trials. We hypothesize the EndoFLIP will serve as a practical drug development tool to provide an objective outcome measures of therapeutic response in EoE clinical trials. We will first validate use of the EndoFLIP in its ability to capture treatment response in a well-defined pediatric EoE population and determine its relationship to other currently available outcome measures (Aim 1). We will then define an approach to pediatric EoE clinical trials using EndoFLIP measurements as an outcome measure by establishing an expected effect size for stratified age groups and treatment duration (Aim 2). This project will provide necessary and sufficient data for designing trials addressing key questions in the treatment of EoE in children. Incorporation of a novel esophageal clinical outcome assessment will fill a critical gap in our current tools available for drug development for this rare disease. The two primary investigators and study sites, both with expertise in EoE, are uniquely suited to accomplish these aims and have successfully partnered to enroll subjects in clinical studies using EndoFLIP and publish original and novel data on the use of EndoFLIP in this patient population.
Eosinophilic esophagitis (EoE) is a rare allergic inflammatory disease that leads to esophageal fibrosis and life- long swallowing dysfunction. Drug development and FDA approval of medications to treat this chronic disease have been stymied by a lack of objective measures of therapeutic response as well as gaps in understanding the natural history of disease; these gaps in clinical trial readiness are even greater for the pediatric population. This proposal seeks to validate the use of esophageal distensibility as a novel clinical outcome measure in a pediatric EoE population, and results from this study will provide the rationale and study design for a well powered EoE clinical trial in children and adolescents with esophageal distensibility as an outcome measure.
