Clinical trial NCT05524844: The Microbiome, Bile Acids, and Notch in Barrett's Esophagus (BE)
Official title: The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Barrett Esophagus
Esophageal Adenocarcinoma
Keywords: Saliva
Microbiome
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: National Cancer Institute (NCI)
First posted: 2022-09-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population will be based on the population of BE and EAC as well as the demographics of those who undergo upper endoscopy for other indications (the control population) at Columbia and Cornell, together with data drawn from numerous prior studies in our BE population.

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.

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

Primary outcomes:
measure: Concentration of Deoxycholic Acid (DCA)
timeFrame: 2 years
measure: Correlation between Enterobacteriaceae (from 16S) and NOTCH3 expression in BE tissue.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Julian Abrams, MD
role: PRINCIPAL_INVESTIGATOR
References: