Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma

NCT ID: NCT00288119

Last Updated: 2025-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-10-01

Study Completion Date

2028-07-31

Brief Summary

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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

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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.

Conditions

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Barrett's Esophagus Esophageal Neoplasm

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Cases

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

Balloon Capsule Device

Intervention Type 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.

Endoscopy

Intervention Type PROCEDURE

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.

EGD Screening

Patients scheduled for clinically indicated EGD for GERD who meet ACG criteria for BE screening

Balloon Capsule Device

Intervention Type 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.

Endoscopy

Intervention Type PROCEDURE

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.

Colon Screening

Patients scheduled for screening colonoscopy who have not had EGD and meet clinically indicated criteria for BE screening

Balloon Capsule Device

Intervention Type 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.

Endoscopy

Intervention Type PROCEDURE

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.

Controls

Patients scheduled for EGD who do not meet criteria for screening

Balloon Capsule Device

Intervention Type 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.

Endoscopy

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type DEVICE

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.

Intervention Type PROCEDURE

Other Intervention Names

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Esophageal Sampling Device BESD-001 EGD

Eligibility Criteria

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Inclusion 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospitals Cleveland Medical Center

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

Mercy Medical Center

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

VA Puget Sound Health Care System

FED

Sponsor Role collaborator

Case Western Reserve University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amitabh Chak, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, CWRU, Cleveland, OH

Gary W Falk, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

William Grady, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center, UWMC, Seattle, WA

Nicholas J Shaheen, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Ganapathy Prasad, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Marcia Canto, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

John Dumont, D.O.

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Prashanthi Thota, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Jean Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Julian Abrams, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Andrew Kaz, MD

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System

Locations

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Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

University Hospitals of Cleveland

Cleveland, Ohio, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

VA Puget Sound Health Care System

Seattle, Washington, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center, UWMC

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Amitabh Chak, MD

Role: CONTACT

216-844-5385

Wendy Brock, RN

Role: CONTACT

216-844-3853

Facility Contacts

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Marcia Canto, M.D.

Role: primary

410-614-5388

Hilary Cosby, RN

Role: backup

(410) 502-2893

Ganapathy A Prasad, M.D.

Role: primary

507-255-6930

Ramona Lansing

Role: backup

507-538-4974

Jean Wang, MD

Role: primary

314-362-5952

Thomas Hollander

Role: backup

314-747-1973

Julian Abrams, MD

Role: primary

212-342-0476

Adriana Rodriquez

Role: backup

212-304-5606

Nicholas J Shaheen, M.D.

Role: primary

919-966-2513

Alondra Santiago

Role: backup

(919) 843-8571

Amitabh Chak, MD

Role: primary

216-844-5386

Wendy Brock, RN

Role: backup

216-844-3853

Prashanthi Thota, MD

Role: primary

216-444-0780

Vidhi Patel, MD

Role: backup

(216) 444-0780

Gary W Falk, MD, MS

Role: primary

215-615-6588

Maureen Demarshall, RN

Role: backup

215-349-8546

Andrew Kaz, MD

Role: primary

Julie LaGuire

Role: backup

206-277-6662

William Grady, MD

Role: primary

206-667-1107

Wynn Burke

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 33493502 (View on PubMed)

Moinova HR, Verma S, Dumot J, Faulx A, Iyer PG, Canto MI, Wang JS, Shaheen NJ, Thota PN, Aklog L, Willis JE, Markowitz SD, Chak A. Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma. Am J Gastroenterol. 2024 Nov 1;119(11):2206-2214. doi: 10.14309/ajg.0000000000002850. Epub 2024 Apr 30.

Reference Type DERIVED
PMID: 38686933 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22178570 (View on PubMed)

Other Identifiers

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NIH IK24DK02800

Identifier Type: -

Identifier Source: secondary_id

R01DK070863

Identifier Type: NIH

Identifier Source: org_study_id

View Link

NCT00058877

Identifier Type: -

Identifier Source: nct_alias

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