Diagnosis and Monitoring of Eosinophilic Esophagitis Using the Cytosponge

Eosinophilic Esophagitis Clinical Trial

Official title: Diagnosis and Monitoring of Eosinophilic Esophagitis Using the Cytosponge

Status Terminated

Clinical Trial Summary

The current endoscopic methods for diagnosing and monitoring treatment response in Eosinophilic Esophagitis (EoE) are costly, inconvenient, and risky. Novel diagnostic methods are needed, and the minimally-invasive Cytosponge holds great promise. It has been shown to be safe and accurate in Barrett's esophagus, it has the advantage (over the string test) of obtaining a true tissue sample, and our preliminary data supports its further study in EoE. The proposed prospective cohort study, conducted by experts in esophageal diseases and EoE, will assess the accuracy of Cytosponge compared to endoscopy and biopsy in EoE, and determine the safety and acceptability of this technique. Use of the Cytosponge would fundamentally change the paradigm for clinical management of EoE by allowing collection of non-endoscopic esophageal biopsies, thus minimizing the need for invasive testing. It would also facilitate future genetic, mechanistic, and pathogenesis research in EoE.

Clinical Trial Description

Study design overview (all Aims) This will be a prospective cohort study, with patient enrollment conducted at UNC and Mayo Clinic with sample analysis performed by the University of Cambridge. In Aim 1, patients with EoE will be enrolled, tissue will be obtained from both the Cytosponge and endoscopy, and the methods will be compared for a single time point to determine accuracy of Cytosponge for quantifying esophageal eosinophil counts. For all patients, safety will be monitored and subjects will complete a survey about the acceptability of Cytosponge (Aim 2).

Cytosponge protocol:

After the study has been explained and a patient provides informed consent, the Cytosponge will be administered prior to endoscopy by trained research staff under physician supervision. If subjects opt to receive a local anesthetic, then they will be provided with a 2% lidocaine gargle prior to administration of the Cytosponge. The Cytosponge will be administered according to it's instructions for use. After retrieval, the string is cut and the sponge (which contains the tissue specimen) is placed in a container, immersed in fixative, and stored in a refrigerator at 4°C. The fixative is then spun in a centrifuge, and the pelleted cells are embedded in a paraffin block using standard techniques.

Upper endoscopy and biopsy:

After the Cytosponge has been removed, the patient will undergo standard of care (routine care) upper endoscopy and biopsy, as clinically indicated. During this exam, research staff will record all endoscopic features of EoE, including rings, furrows, white plaques, decreased vascularity, and strictures. The severity of the endoscopy findings will be measured using the recently validated endoscopic reference score (EREFS) scoring system. Four esophageal biopsies will be taken both from the distal (5 cm above the gastro-esophageal junction) and proximal (15 cm above the gastro-esophageal junction) esophagus. This number of biopsies has been shown to maximize the diagnostic sensitivity for EoE.

Histology and eosinophil counts:

All tissue samples from the Cytosponge and endoscopy will be coded with a subject's identification number, but will otherwise be masked for all clinical data, including EoE activity, symptoms, patient characteristics, and treatments prescribed. Using the paraffin blocks, pathology slides will be cut and the tissue processed with routine H&E staining. The slides will then be digitized, and using the Aperio ImageScope (Aperio Technologies, Vista, CA), the maximum eosinophil density (eosinophils/mm2 [eos/mm2]) will be determined using our previously validated protocol. For purposes of comparison to previous studies, eosinophil density will then be converted to eosinophil counts (eos/hpf) for an assumed hpf size of 0.24 mm2, the size of an average field as reported in the literature. The study pathologists from UNC and Mayo Clinic will review the specimens from their sites, and the study pathology from Cambridge will provide a second review of all specimens to ensure the most accurate quantification of eosinophil counts possible.

In addition, investigators plan to perform special staining and analysis of the existing biopsy and sponge samples with the goal of determining if the diagnostic accuracy of this test can be improved. In particular investigators will examine markers of eosinophil function, activation, and inflammation, such as eosinophil peroxidase (EPX), a granule protein that clearly identifies intact eosinophils, as well as extracellular EPX deposition suggestive of degranulation. This can be detected with immunohistochemistry. This would be done at Mayo clinic with our current collaborators who currently have the coded specimens.

Safety and accessibility assessments:

Patients will be assessed at multiple points to determine the safety of the Cytosponge in EoE. Investigators will assess for any symptoms or events as soon as the sponge capsule is swallowed, as well as immediately after the expanded sponge is removed. Participants will be contacted 1 and 7 days after the endoscopy to assess for adverse events. For Aim 2, participants will be administered the acceptability survey at the 7 day follow-up point, so patients have adequate time to reflect on their experiences with both tissue collection approaches. In particular this survey will record the patient's experience with swallowing the Cytosponge, whether they would do it again, and whether they prefer the Cytosponge or endoscopy for diagnosis and monitoring of EoE. ;

Related Conditions & MeSH terms

• EoE
• Eosinophilic Esophagitis
• Esophagitis

• NCT number: NCT02114606
• Study type: Interventional
• Source: University of North Carolina, Chapel Hill
• Status: Terminated
• Phase: N/A
• Start date: July 2015
• Completion date: June 2016