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

• ClinicalTrials.gov Identifier: NCT00288119
• Recruitment Status: Recruiting
• First Posted: February 7, 2006
• Last Update Posted: May 9, 2024
• Sponsor: Case Western Reserve University
• Collaborators: University Hospitals Cleveland Medical Center; Washington University School of Medicine; Fred Hutchinson Cancer Center; University of Washington; Mercy Medical Center; Johns Hopkins University; Mayo Clinic; University of North Carolina, Chapel Hill; The Cleveland Clinic; University of Pennsylvania; Columbia University; VA Puget Sound Health Care System
• Information provided by (Responsible Party): Case Western Reserve University

Tracking Information

• First Submitted Date: February 6, 2006
• First Posted Date: February 7, 2006
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: October 1, 2005
• Estimated Primary Completion Date: July 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2021)

Assay of DNA and RNA markers [ Time Frame: 1 week ]

The Balloon tip is collected and sent to the PacificDx Laboratory in Irvine California to test for DNA extraction

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: June 28, 2018)

Score of tolerability and acceptability [ Time Frame: 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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma
• Official Title: Genetic and Environmental Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

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 Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood Samples from + families with 3 or members diagnosed with BE or ECA will be sent to our NIH approved Biorepository and this repository is designed to help all researchers performing studies on the genetic basis of diseases.

Biospecimens, brushings and biopsies, will be obtained via snap frozen at bedside and stored for future research assays at Case Western Reserve Biorepository.

Balloon Capsule Device Tips are sent to the University Hospitals Transnational Laboratory in Cleveland. The tips are processed for process of assay of DNA and RNA.

• 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.

Condition

• Barrett's Esophagus
• Esophageal Neoplasm

Intervention

• 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 Name: 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 Name: EGD

Study Groups/Cohorts

• Cases
  Patients with Barrett's esophagus undergoing surveillance or patients with esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma undergoing EGD
  Interventions:

  • Device: Balloon Capsule Device
  • Procedure: Endoscopy
• EGD Screening
  Patients scheduled for clinically indicated EGD for GERD who meet ACG criteria for BE screening
  Interventions:

  • Device: Balloon Capsule Device
  • Procedure: Endoscopy
• Colon Screening
  Patients scheduled for screening colonoscopy who have not had EGD and meet clinically indicated criteria for BE screening
  Interventions:

  • Device: Balloon Capsule Device
  • Procedure: Endoscopy
• Controls
  Patients scheduled for EGD who do not meet criteria for screening
  Interventions:

  • Device: Balloon Capsule Device
  • Procedure: Endoscopy

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 21, 2023): 2000
• Original Enrollment (submitted: February 6, 2006): 1000
• Estimated Study Completion Date: July 31, 2028
• Estimated Primary Completion Date: July 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Amitabh Chak, MD; 216-844-5385; axc22@po.cwru.edu

Contact: Wendy Brock, RN; 216-844-3853; wendy.brock@UHhospitals.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00288119
• Other Study ID Numbers: R01DK070863( U.S. NIH Grant/Contract ); NIH IK24DK02800
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Case Western Reserve University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Case Western Reserve University
• Original Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborators

• University Hospitals Cleveland Medical Center
• Washington University School of Medicine
• Fred Hutchinson Cancer Center
• University of Washington
• Mercy Medical Center
• Johns Hopkins University
• Mayo Clinic
• University of North Carolina, Chapel Hill
• The Cleveland Clinic
• University of Pennsylvania
• Columbia University
• VA Puget Sound Health Care System

Investigators

• Principal Investigator: Amitabh Chak, MD; University Hospitals Cleveland Medical Center, CWRU, Cleveland, OH
• Principal Investigator: Gary W Falk, MD, MS; University of Pennsylvania
• 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: Julian Abrams, MD; Columbia University
• Principal Investigator: Andrew Kaz, MD; VA Puget Sound Health Care System

• PRS Account: Case Western Reserve University
• Verification Date: May 2024