The Microbiome, Bile Acids, and Notch in Barrett's Esophagus (BE)

NCT ID: NCT05524844

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 54 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-02-09
• Study Completion Date: 2024-11-01

Brief Summary

The purpose of this study is to prospectively collect and analyze clinical data and biospecimens from a cohort of 100 patients without BE (20), with non-dysplastic BE (40), or with BE and high grade dysplasia (HGD) or EAC (40). The investigators will enroll 80 patients scheduled for upper endoscopy for clinical purposes, with a history of histologically confirmed BE (2 cm length); 40 with no history of dysplasia, and 40 with HGD or EAC. The investigators will also enroll 20 non-BE controls undergoing endoscopy for any indication who are on stable dose proton-pump inhibitors (PPI) for the past month. PPI therapy is standard of care for BE patients.

Detailed Description

The incidence of esophageal adenocarcinoma (EAC) has risen 10-fold over the past half century and continues to have a dismal prognosis. Known risk factors for EAC do not adequately explain these incidence trends; the rise in EAC cases began a decade before increases in the prevalence of both gastro-esophageal reflux disease and obesity. Over the past 50+ years, dramatic changes in the bacterial composition (or microbiome) of the upper gastrointestinal tract have also occurred. While prior work has shown correlations between the microbiome, BE, and EAC, there is a critical knowledge gap on mechanisms by which bacteria interact with the esophagus and potentially promote cancer. The investigators hypothesize that increased levels of the certain bile acids in gastroesophageal reflux fluid cause changes that lead to increased interaction between bacteria and the esophagus, which may promote the development of esophageal adenocarcinoma (EAC). The investigators will carry out a case-control study of patients with and without BE, dysplasia, or EAC. The investigators will focus on deoxycholic acid in gastro-esophageal refluxate and its association with Notch signaling in tissue and bacterial composition. The microbiome represents a novel and potentially modifiable risk factor for the development of BE and EAC. Elucidation of microbiome features and mechanisms that promote the development of EAC is a critical step that will lead to subsequent trials of antibiotics, probiotics, and other interventions targeted to altering the microbiome, with the goal of lowering the risk of this highly lethal malignancy.

Conditions

Barrett Esophagus; Esophageal Adenocarcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Control

Non-BE controls undergoing endoscopy for any indication who are on stable dose Proton Pump Inhibitors for the past month.

Sample Collection

Intervention Type: OTHER

Saliva, gastric aspirate, and esophageal brushings and biopsies.

Endoscopy results

Intervention Type: OTHER

Results from standard of care endoscopy (scheduled separate of study)

Dietary questionnaire

Intervention Type: OTHER

Diet History Questionnaire (II)

Barrett's Esophagus

Patients scheduled for upper endoscopy for clinical purposes, with a history of histologically confirmed Barrett's esophagus (2 cm length); 40 with no history of dysplasia, and 40 with high grade dysplasia or esophageal adenocarcinoma.

Sample Collection

Intervention Type: OTHER

Saliva, gastric aspirate, and esophageal brushings and biopsies.

Endoscopy results

Intervention Type: OTHER

Results from standard of care endoscopy (scheduled separate of study)

Dietary questionnaire

Intervention Type: OTHER

Diet History Questionnaire (II)

Interventions

Sample Collection

Saliva, gastric aspirate, and esophageal brushings and biopsies.

Intervention Type: OTHER

Endoscopy results

Results from standard of care endoscopy (scheduled separate of study)

Intervention Type: OTHER

Dietary questionnaire

Diet History Questionnaire (II)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

All subjects:

• Scheduled for an upper endoscopy
• Taking stable dose of a proton pump inhibitor at least once daily for 1 months prior to enrollment
• Eighteen years of age or older
• Able to give informed consent

Barrett's esophagus subjects only:

• Histologically confirmed BE (defined as endoscopically- suspected BE with intestinal metaplasia with goblet cells on esophageal biopsies)
• Maximal BE length ≥ 2 cm (Prague criteria: any C, M≥2)

Exclusion Criteria

All subjects:

• History of head and neck cancer or esophageal or gastric cancer (except esophageal intramucosal adenocarcinoma)
• History of esophageal or gastric surgery
• Use of antibiotics or immunosuppressants within 1 month prior to endoscopy

Barrett's esophagus subjects only:

• History of prior endoscopic therapy for BE, except a history of prior endoscopic mucosal resection (EMR) of focal lesions withoutsubsequent ablative therapy is permitted

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Julian A Abrams, MD

Associate Professor of Medicine and Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julian Abrams, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Weill Cornell Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

R01CA255298

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAT2456

Identifier Type: -

Identifier Source: org_study_id