Diagnosis and Monitoring of Eosinophilic Esophagitis Using the Cytosponge

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

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. In Aim 2, the patients who are being treated will be followed and tissue will be assessed over time with both Cytosponge and endoscopy to determine the utility of Cytosponge for monitoring treatment response in patients with EoE. For all patients, safety will be monitored and subjects will complete a survey about the acceptability of Cytosponge (Aim 3). Cytosponge protocol: After the study has been explained and a patient provides informed consent, the Cytosponge will be administered prior to endoscopy by the research coordinator under physician supervision. The string, attached to a 3-inch cardboard tab, will be held loosely at the mouth by the coordinator, and the subject will swallow the sponge capsule with an ounce of water. The string will be held without tension to allow the capsule to advance into the stomach. Five minutes after ingestion, the back of the throat will be sprayed with 1% lidocaine spray, and the expanded sponge withdrawn by gentle traction on the string. 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, we 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 EREFS scoring system.23 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.24 Histology and eosinophil counts: All tissue samples from the Cytosponge and endoscopy will be coded with a subject's ID 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.25 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.26 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. Safety and accessibility assessments: Patients will be assessed at multiple points to determine the safety of the Cytosponge in EoE. We 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. We will also contact them 1 and 7 days after the endoscopy to assess for adverse events. For Aim 3, we will administer 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.

Who is eligible to participate?

Inclusion Criteria: - Male or female subjects, age 18-80 years, - Diagnosis of EoE with current active disease, - Have previously and recently received an upper endoscopy during which absence of findings putting the subject at higher risk for these theoretical concerns (conditions such as varices and stricture) will be documented. Exclusion Criteria: - History of esophageal stricture precluding passage of the endoscope or sponge, - Pregnancy, or planned pregnancy during the course of the study, - Any history of esophageal varices, liver impairment of moderate or worse severity (Child's- Pugh class B & C) or evidence of varices noted on any past endoscopy, - Any history of esophageal surgery, except for uncomplicated fundoplication - History of coagulopathy, with INR>1.3 and/or platelet count of <75,000. - Are not able to discontinue blood thinning medications such as aspirin, clopidogrel, and/or warfarin for 5 days prior and 7 days after procedures, - Are allergic to local anesthetics such as lidocaine, - Have not fasted the night before administration of the Cytosponge.

Last updated:

6/16/2014

NCT ID:

NCT02114606

IRB Number:

11-006429