Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

Recruiting

• Conditions: Esophageal Neoplasm; Barrett's Esophagus

• Registration Number: NCT00288119
• Lead Sponsor: Case Western Reserve University

Brief Summary

The overall objectives of this BETRNet Research Center (RC) are:

1. to conduct a rigorous, integrated spectrum of transdisciplinary human research in Barrett's esophagus (BE) and esophageal adenocarcinoma (ECA)

2. to increase the biological understanding of key observations made by our clinical researchers;

3. to translate knowledge derived from genetic, epigenetic, and transcriptome research to solving clinical dilemmas in detection, prognosis, prevention, and therapy of BE in order to prevent EAC and improve the outcomes of EAC;

4. to foster a transdisciplinary and translation research culture and to effectively expand and enhance scientific research focused on BE and EAC;

5. to evaluate research and transdisciplinary programs and to continuously improve research, productivity and enhance translational implementation. These objectives build and synergize on existing multi-institutional collaborative networks and the considerable clinical, basic science, and translational expertise available at our institutions, focusing on improving the outcomes of patients with BE and EAC. The overarching organization framework for this RC proposal is 1) to focus laboratory research on understanding the genetic susceptibility, genomic and epigenetic changes that influence the development of BE and EAC; and 2) to then translate laboratorydiscoveries into clinical applications for effective detection, molecular risk stratification, and prevention of progression from BE to EAC.

Detailed Description

This research will eventually lead to the identification of inherited genetic changes that cause Barrett's esophagus and esophageal cancer. It will help the investigators develop better methods for preventing or identifying esophageal cancer at an early curable stage.

The capsule can be swallowed with a few sips water. Once the capsule is advanced to 45-50 cm from the incisors and reaches the stomach the balloon is inflated to a size of 16 mm with 5.5 cc air. It is withdrawn until a tug is felt to locate the gastroesophageal junction (GEJ). The inflated balloon is then pulled back 3 to 5 cm to sample the distal esophagus, then completely deflated to cause inversion of the biospecimen into its protective capsule, and then withdrawn. The balloon is re-inflated outside the patient and the obtained sample is clipped with scissors into a vial and frozen. The collected biospecimen will be stored frozen for later DNA extraction and assay. The vials will be labeled with a coded sample number. In a pilot study of 120 subjects this capsule esophageal sampling was performed with no adverse events reported. Similar esophageal sampling devices have been reported on over 1600 patients with no adverse events.

All patients will also undergo standard EGD. Patients with BE or EAC will have standard of care surveillance and diagnostic biopsies. All cases and controls will have research esophageal brushings from the BE/EAC and distal esophagus/gastric cardia, respectively. Cases and controls will also obtain research brushings from the proximal normal squamous esophagus. Research mucosal biopsies will also be obtained from the BE and EAC epithelium as well as normal stomach and duodenum in cases and from the gastric cardia and the distal squamous esophagus as well as normal stomach and duodenum in controls. Biopsies from BE and EAC will be directed by using high definition narrow band imaging. Biospecimens, brushings and biopsies, will be snap frozen at bedside and stored for future research assays. Although we do not anticipate any problems with our non-endoscopic balloon screening, these archived pathology samples and snap frozen samples will be available for assay in case we fail to detect our markers in patients with BE diagnosed at EGD or experience a high false positive rate. Subjects who undergo non-endoscopic sampling of the distal esophagus will be asked questions that rate their discomfort on a Likert scale and also asked questions comparing the non-endoscopic sampling study with an EGD.

Study Timeline

• Study Start: 2005-10-01
• Study First Submitted: 2006-02-06
• Study First Submitted QC: 2006-02-06
• Study First Posted: 2006-02-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-22
• Primary Completion: 2028-07-31
• Study Completion: 2028-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assay of DNA and RNA markers	1 week	The Balloon tip is collected and sent to the PacificDx Laboratory in Irvine California to test for DNA extraction

Secondary Outcome Measures

Name	Time	Method
Score of tolerability and acceptability	1 minute after procedure	6 item scale rating scale using scale of 1-10 where 1 is no worries to 10 being severe to rate Tolerability; and a 3 item scale rating the acceptability of Balloon Capsule Device using strongly agree to strongly disagree rating

Trial Locations

Locations (10)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

University Hospitals of Cleveland; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

VA Puget Sound Health Care System; 🇺🇸 Seattle, Washington, United States

Fred Hutchinson Cancer Research Center, UWMC; 🇺🇸 Seattle, Washington, United States