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

Barrett Esophagus Clinical Trial

Official title:

The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05524844
• Other study ID #: AAAT2456
• Secondary ID: R01CA255298
• Status: Recruiting
• Start date: February 9, 2021
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Columbia University
• Contact: Julian Abrams, MD
• Phone: 2128059541
• Email: ja660[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Barrett Esophagus
• Esophageal Adenocarcinoma
• Esophageal Neoplasms

Intervention

Other:
• Sample Collection
Saliva, gastric aspirate, and esophageal brushings and biopsies.
• Endoscopy results
Results from standard of care endoscopy (scheduled separate of study)
• Dietary questionnaire
Diet History Questionnaire (II)

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York
United States	Weill Cornell Medical Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	National Cancer Institute (NCI), Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of Deoxycholic Acid (DCA)	To determine whether refluxate deoxycholic acid (DCA) is associated with increased Notch signaling in the development of esophageal adenocarcinoma (EAC), the investigators will calculate Pearson's correlation coefficients to assess within individual correlations between DCA and NOTCH3 gene expression.	2 years
Primary	Correlation between Enterobacteriaceae (from 16S) and NOTCH3 expression in BE tissue.	The within-individual correlation will be calculated.	2 years