Clinical trial NCT02114606: Diagnosis and Monitoring of Eosinophilic Esophagitis Using the Cytosponge
Official title: Diagnosis and Monitoring of Eosinophilic Esophagitis Using the Cytosponge
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Eosinophilic Esophagitis
EoE
Keywords: Eosinophilic Esophagitis
EoE
Cytosponge
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: University of Cambridge
name: CURED Foundation
First posted: 2014-04-15
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Able to read, comprehend, and complete the informed consent form
* Male or female subjects, age 18-80 years,
* Suspected EoE or has a diagnoses of EoE with current active disease,

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 international normalized ratio (INR) \>1.3 and/or platelet count of \<75,000.
* Current use of blood thinners such as coumadin, warfarin, clopidogrel, heparin and/or low molecular weight heparin (requires discontinuation of medication 7 days prior to and 7 days after esophagogastroduodenoscopy (EGD) and Cytosponge administration, aspirin use is OK).
* Are allergic to local anesthetics such as lidocaine (these subjects may opt not to receive the optional lidocaine gargle prior to the Cytosponge administration and still be eligible).
* Have not fasted the night before administration of the Cytosponge.
* History of perforation

Primary outcomes:
measure: Percent Agreement Between Cytosponge and Endoscopic Biopsy Results
timeFrame: At study enrollment and initial procedure and each additional procedure, up to 1 year after enrollment
Secondary outcomes:
measure: Overall Agreement Between Cytosponge and Endoscopic Biopsy Results as Measured by Kappa
timeFrame: At study enrollment and initial procedure and each additional procedure, up to 1 year after enrollment
measure: Acceptability of Cytosponge Compared to Endoscopic Biopsy, as Measured by Visual Analog Scale
timeFrame: 7 days after each procedure
measure: Acceptability of Cytosponge as Measured by the Impact of Events Scale
timeFrame: 7 days after each procedure
Other outcomes:
measure: Number of Responses Indicating Preference for Cytosponge Over Endoscopic Biopsy
timeFrame: 7 days after each procedure
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC-Chapel Hill
name: Evan Dellon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hirano I, Moy N, Heckman MG, Thomas CS, Gonsalves N, Achem SR. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013 Apr;62(4):489-95. doi: 10.1136/gutjnl-2011-301817. Epub 2012 May 22.
citation: Gonsalves N, Policarpio-Nicolas M, Zhang Q, Rao MS, Hirano I. Histopathologic variability and endoscopic correlates in adults with eosinophilic esophagitis. Gastrointest Endosc. 2006 Sep;64(3):313-9. doi: 10.1016/j.gie.2006.04.037.
citation: Dellon ES, Fritchie KJ, Rubinas TC, Woosley JT, Shaheen NJ. Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia. Dig Dis Sci. 2010 Jul;55(7):1940-9. doi: 10.1007/s10620-009-1005-z. Epub 2009 Oct 15.
citation: Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ. Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review. Am J Gastroenterol. 2007 Oct;102(10):2300-13. doi: 10.1111/j.1572-0241.2007.01396.x. Epub 2007 Jul 7.
citation: Katzka DA, Smyrk TC, Alexander JA, Geno DM, Beitia RA, Chang AO, Shaheen NJ, Fitzgerald RC, Dellon ES. Accuracy and Safety of the Cytosponge for Assessing Histologic Activity in Eosinophilic Esophagitis: A Two-Center Study. Am J Gastroenterol. 2017 Oct;112(10):1538-1544. doi: 10.1038/ajg.2017.244. Epub 2017 Aug 15.