Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma (FBE)

Genetic and Environmental Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Barrett's Esophagus; Esophageal Neoplasm
• Intervention / Treatment: Device: Balloon Capsule Device; Procedure: Endoscopy

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 It is withdrawn until a tug is felt to locate the gastroesophageal junction (GEJ).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 Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Wendy Brock, RN; Phone Number: 216-844-3853; Email: wendy.Brock@UHhospitals.org
• Study Contact Backup: Name: Amitabh Chak, MD; Phone Number: 216-844-5385; Email: axc22@po.cwru.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Marcia Canto, M.D.; Phone Number: 410-614-5388
      • Contact: Hilary Cosby, RN; Phone Number: (410) 502-2893; Email: Hcosby1@jhmi.edu
      • Principal Investigator: Marcia I Canto, M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Ganapathy A Prasad, M.D.; Phone Number: 507-255-6930; Email: Prasad.Ganapathy@Mayo.edu
      • Contact: Ramona Lansing; Phone Number: 507-538-4974; Email: lansing.ramona@mayo.edu
      • Principal Investigator: Ganapathy A Prasad, M.D.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Jean Wang, MD; Phone Number: 314-362-5952; Email: jwang@DOM.wustl.edu
      • Contact: Thomas Hollander; Phone Number: 314-747-1973; Email: tholland@DOM.wustl.edu
      • Principal Investigator: Jean Wang, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Julian Abrams, MD
      • Contact: Julian Abrams, MD; Phone Number: 212-342-0476; Email: ja660@mail.cumc.columbia.edu
      • Contact: Adriana Rodriquez; Phone Number: 212-304-5606
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Nicholas J Shaheen, M.D.; Phone Number: 919-966-2513; Email: nshaheen@med.unc.edu
      • Contact: Alondra Santiago; Phone Number: (919) 843-8571; Email: alondra_santiago@med.unc.edu
      • Principal Investigator: Nicholas J Shaheen, M.D.
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Prashanthi Thota, MD; Phone Number: 216-444-0780; Email: THOTAP@ccf.org
      • Contact: Vidhi Patel, MD; Phone Number: (216) 444-0780; Email: VPatel@ccf.org
      • Principal Investigator: Prashanthi Thota, MD
    • Cleveland, Ohio, United States, 44106-8066
      • Recruiting
      • University Hospitals Of Cleveland
      • Contact: Wendy Brock, RN; Phone Number: 216-844-3853; Email: wendy.Brock@UHhospitals.org
      • Principal Investigator: Amitabh Chak, MD
      • Sub-Investigator: John Dumot, MD
      • Contact: Amitabh Chak, MD; Phone Number: 216-844-5386; Email: axc22@po.cwru.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Gary W Falk, MD, MS; Phone Number: 215-615-6588; Email: Gary.Falk@uphs.upenn.edu
      • Contact: Maureen Demarshall, RN; Phone Number: 215-349-8546; Email: demarchm@mail.upenn.edu
      • Principal Investigator: Gary W. Falk, MD, MS
  • Washington
    • Seattle, Washington, United States, 98108
      • Recruiting
      • VA Puget Sound Health Care System
      • Contact: Andrew Kaz, MD
      • Contact: Julie LaGuire; Phone Number: 206-277-6662; Email: julie.laguire@VA.gov
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center, UWMC
      • Contact: William Grady, MD; Phone Number: 206-667-1107; Email: wgrady@fhcrc.org
      • Contact: Wynn Burke; Email: WBurke@medicine.washington.edu
      • Principal Investigator: William Grady, MD
      • Principal Investigator: Kaz Andrew, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Individuals with Barrett's esophagus or adenocarcenoma of the esophagus whose medical care is at the participating institutions, are referred from outside institutions, or who contact the participating institutions.

Description

Eligible cases will be defined as those patients and their family members who meet the following criteria:

• Barrett's esophagus confirmed by review of pathology and endoscopy report or adenocarcinoma of the esophagus or family members of person with Barrett's esophagus or adenocarcinoma of the esophagus.
• Male or female age 18 or older at time of enrollment or male or female less than 18 years of age at time of enrollment with parental consent.
• Ability to give informed consent, if patient is age 18 or older.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Patients with Barrett's esophagus undergoing surveillance or patients with esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma undergoing EGD	Device: Balloon Capsule Device; The Esophageal Sampling Device BESD-001 is a non-endoscopic balloon capsule catheter for obtaining an esophageal mucosal sample. At the distal end of the catheter there is a silicone capsule textured balloon assembly. The textured balloon is initially inverted with vacuum for patient to swallow the capsule but then is inflated with 5.6 cc of air (5 cc syringe withdrawn maximally) to a 16-18 mm diameter in order to contact the lumen of the esophagus to collect a sample. The balloon has a textured surface, which enhances the collection of the esophageal sample. Following sample collection the textured balloon is inverted back into the hollow capsule component via syringe draw vacuum in order to maximize & protect the site-specific sample collection.; Other Names: Esophageal Sampling Device BESD-001; Procedure: Endoscopy; An upper endoscopy is a procedure used to visually examine your upper digestive system with a tiny camera on the end of a long, flexible tube.; Other Names: EGD
EGD Screening; Patients scheduled for clinically indicated EGD for GERD who meet ACG criteria for BE screening	Device: Balloon Capsule Device; The Esophageal Sampling Device BESD-001 is a non-endoscopic balloon capsule catheter for obtaining an esophageal mucosal sample. At the distal end of the catheter there is a silicone capsule textured balloon assembly. The textured balloon is initially inverted with vacuum for patient to swallow the capsule but then is inflated with 5.6 cc of air (5 cc syringe withdrawn maximally) to a 16-18 mm diameter in order to contact the lumen of the esophagus to collect a sample. The balloon has a textured surface, which enhances the collection of the esophageal sample. Following sample collection the textured balloon is inverted back into the hollow capsule component via syringe draw vacuum in order to maximize & protect the site-specific sample collection.; Other Names: Esophageal Sampling Device BESD-001; Procedure: Endoscopy; An upper endoscopy is a procedure used to visually examine your upper digestive system with a tiny camera on the end of a long, flexible tube.; Other Names: EGD
Colon Screening; Patients scheduled for screening colonoscopy who have not had EGD and meet clinically indicated criteria for BE screening	Device: Balloon Capsule Device; The Esophageal Sampling Device BESD-001 is a non-endoscopic balloon capsule catheter for obtaining an esophageal mucosal sample. At the distal end of the catheter there is a silicone capsule textured balloon assembly. The textured balloon is initially inverted with vacuum for patient to swallow the capsule but then is inflated with 5.6 cc of air (5 cc syringe withdrawn maximally) to a 16-18 mm diameter in order to contact the lumen of the esophagus to collect a sample. The balloon has a textured surface, which enhances the collection of the esophageal sample. Following sample collection the textured balloon is inverted back into the hollow capsule component via syringe draw vacuum in order to maximize & protect the site-specific sample collection.; Other Names: Esophageal Sampling Device BESD-001; Procedure: Endoscopy; An upper endoscopy is a procedure used to visually examine your upper digestive system with a tiny camera on the end of a long, flexible tube.; Other Names: EGD
Controls; Patients scheduled for EGD who do not meet criteria for screening	Device: Balloon Capsule Device; The Esophageal Sampling Device BESD-001 is a non-endoscopic balloon capsule catheter for obtaining an esophageal mucosal sample. At the distal end of the catheter there is a silicone capsule textured balloon assembly. The textured balloon is initially inverted with vacuum for patient to swallow the capsule but then is inflated with 5.6 cc of air (5 cc syringe withdrawn maximally) to a 16-18 mm diameter in order to contact the lumen of the esophagus to collect a sample. The balloon has a textured surface, which enhances the collection of the esophageal sample. Following sample collection the textured balloon is inverted back into the hollow capsule component via syringe draw vacuum in order to maximize & protect the site-specific sample collection.; Other Names: Esophageal Sampling Device BESD-001; Procedure: Endoscopy; An upper endoscopy is a procedure used to visually examine your upper digestive system with a tiny camera on the end of a long, flexible tube.; Other Names: EGD

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score of tolerability and acceptability	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	1 minute after procedure

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: Johns Hopkins University; Mayo Clinic; University of Pennsylvania; Washington University School of Medicine; Columbia University; The Cleveland Clinic; University of Washington; Fred Hutchinson Cancer Center; University of North Carolina, Chapel Hill; Case Western Reserve University; VA Puget Sound Health Care System; Mercy Medical Center
• Investigators: Principal Investigator: Gary W Falk, MD, MS, University of Pennsylvania; Principal Investigator: Amitabh Chak, MD, University Hospitals Cleveland Medical Center, CWRU, Cleveland, OH; Principal Investigator: William Grady, MD, Fred Hutchinson Cancer Research Center, UWMC, Seattle, WA; Principal Investigator: Nicholas J Shaheen, M.D., University of North Carolina, Chapel Hill; Principal Investigator: Ganapathy Prasad, M.D., Mayo Clinic; Principal Investigator: Marcia Canto, M.D., Johns Hopkins University; Principal Investigator: John Dumont, D.O., University Hospitals Cleveland Medical Center; Principal Investigator: Prashanthi Thota, M.D., The Cleveland Clinic; Principal Investigator: Jean Wang, MD, Washington University School of Medicine; Principal Investigator: Andrew Kaz, MD, VA Puget Sound Health Care System; Principal Investigator: Julian Abrams, MD, Columbia University

Publications and helpful links

General Publications

• Douville C, Moinova HR, Thota PN, Shaheen NJ, Iyer PG, Canto MI, Wang JS, Dumot JA, Faulx A, Kinzler KW, Papadopoulos N, Vogelstein B, Markowitz SD, Bettegowda C, Willis JE, Chak A. Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus. Gastroenterology. 2021 May;160(6):2043-2054.e2. doi: 10.1053/j.gastro.2021.01.209. Epub 2021 Jan 22.
• Chak A, Chen Y, Vengoechea J, Canto MI, Elston R, Falk GW, Grady WM, Guda K, Kinnard M, Markowitz S, Mittal S, Prasad G, Shaheen N, Willis JE, Barnholtz-Sloan JS. Variation in age at cancer diagnosis in familial versus nonfamilial Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):376-83. doi: 10.1158/1055-9965.EPI-11-0927. Epub 2011 Dec 16.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2005
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimated): February 7, 2006

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Barrett's Esophagus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Precancerous Conditions; Adenocarcinoma; Esophageal Neoplasms; Barrett Esophagus
• Other Study ID Numbers: R01DK070863 (U.S. NIH Grant/Contract); NIH IK24DK02800

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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