The Microenvironment in Barrett's Esophagus (BETRNet2)

Application of the Microbiome and Microenvironment to Novel Non-Endoscopic Screening and Surveillance in Barrett's Esophagus

This study aims to elucidate the relationship between the microbiome, inflammation, and the microenvironment in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with the end goal of developing a non-endoscopic testing strategy based on pathogenic factors to identify patients at highest risk for EAC. To accomplish this the investigators will enroll 100 patients with known BE (50 with dysplasia or EAC) and 50 subjects without BE undergoing upper endoscopy. Prior to endoscopy each subject will undergo three minimally invasive potential screening and surveillance tests: saliva (oral microbiome), breath test (exhaled volatile organic compounds), and tethered capsule sponge sampling (methylated DNA markers). The study will evaluate these novel tests in combination with clinical and anthropometric factors to describe an optimal strategy for BE screening and monitoring.

Study Overview

• Status: Completed
• Conditions: Barrett Esophagus; Esophageal Adenocarcinoma
• Intervention / Treatment: Device: Tethered capsule sponge; Device: Electronic nose device

Detailed Description

The investigators will perform a multi-center cross-sectional study of patients with Barrett's esophagus, with and without associated dysplasia or cancer, and controls without BE. Enrollment of controls will be stratified based on use of proton pump inhibitors (PPIs). The investigators plan to enroll an approximate total of 150 subjects:

100 BE patients (with or without associated dysplasia or cancer)

• 50 subjects with non-dysplastic BE

• 50 subjects with BE and dysplasia or EAC

  50 controls

• 25 controls on PPIs (at least once daily)
• 25 controls not taking PPIs

Various tests will be performed and samples collected on the day of endoscopy. These tests include: saliva samples, electronic nose device testing, tethered capsule sponge testing, dietary questionnaires, and collection of blood and gastrointestinal biosamples. Analyses of this data and samples will then be performed to address the specific aims above.

• Study Type: Observational
• Enrollment (Actual): 155

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with or without Barrett's esophagus already scheduled for upper endoscopy.

Description

Inclusion Criteria:

(for BE patients)

• History of histologically confirmed BE, defined as endoscopically-suspected BE with intestinal metaplasia with goblet cells on esophageal biopsies
• BE length M≥2
• Taking proton pump inhibitors at least once daily for 3 months prior to enrollment
• Age ≥18

Exclusion Criteria:

• History of gastric cancer or esophageal squamous cell cancer
• History of gastric or esophageal surgery
• Use of antibiotics or systemic immunosuppressants within three months prior to the date of endoscopy (intranasal and inhaled steroids are allowed)
• Known untreated esophageal stricture or uninvestigated dysphagia
• Inability to give informed consent
• (BE patients only) History of prior endoscopic therapy for BE except a history of prior endoscopic mucosal resection (EMR) of focal lesions without subsequent ablative therapy is permitted

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Barrett's esophagus; Barrett's esophagus, without or with dysplasia or adenocarcnoma	Device: Tethered capsule sponge; Subjects swallow a tethered capsule sponge sampling device, which is then withdrawn through the mouth after an interval of 5 minutes.; Other Names: EsophaCap; Device: Electronic nose device; Subjects breathe into the device, which then records an exhaled volatile organic compounds (VOC) signature.; Other Names: Aeonose
Controls; Non-BE endoscopic controls	Device: Tethered capsule sponge; Subjects swallow a tethered capsule sponge sampling device, which is then withdrawn through the mouth after an interval of 5 minutes.; Other Names: EsophaCap; Device: Electronic nose device; Subjects breathe into the device, which then records an exhaled volatile organic compounds (VOC) signature.; Other Names: Aeonose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral and esophageal 16S rRNA gene sequencing	Oral and esophageal microbiome	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Esophageal tissue RNA-Seq	Esophageal tissue transcriptome	1 day
Gastric aspirate mass spectrometry	Gastric aspirate bile acid composition	1 day

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Mayo Clinic; University of Pennsylvania
• Investigators: Principal Investigator: Julian A. Abrams, MD, MS, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Microbiome; Screening; Barrett Esophagus; Esophageal Adenocarcinoma; Microenvironment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Adenocarcinoma; Barrett Esophagus
• Other Study ID Numbers: AAAQ8763; NCI U54 CA163004-09 (Other Identifier: National Cancer Institute/NIH/ DHHS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No