Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition

Dallas VA Medical Center

Status: Completed

Conditions: Gastroesophageal Reflux Disease; Barrett's Esophagus

Treatments: Other: Cessation of Acid Suppressing Medications

Study type: Interventional

Funder types: Other U.S. Federal agency; NIH

Identifiers

NCT02579460

1R01DK103598-01A1 (U.S. NIH Grant/Contract)

15-022

Details and patient eligibility

About

The purpose of this study is to elucidate mechanisms whereby oxidative stress induced by acute reflux esophagitis: 1) activates p38 to regulate proteins that control the G1/S cell cycle checkpoint, and 2) activates HIFs (hypoxia inducible factors) to cause autocrine VEGF (vascular endothelial growth factor) signaling that triggers the EMT (epithelial-mesenchymal-transition) program in Barrett's esophagus.

Full description

Gastroesophageal reflux disease (GERD) and its complication, Barrett's esophagus (BE), are risk factors for esophageal adenocarcinoma. In BE, GERD causes inflammation with oxidative DNA damage and genomic instability that contributes to carcinogenesis. In BE, one response to oxidative stress is p38 pathway activation, which might protect against cancer development by initiating G1 arrest and enabling repair of DNA damage. Inflammation and oxidative stress also might induce epithelial-mesenchymal transition (EMT), the process in which epithelial cells acquire mesenchymal characteristics including the ability to migrate. This study will elucidate mechanisms whereby the oxidative stress of acute reflux esophagitis in BE activates p38 to regulate proteins controlling the G1/S cell cycle checkpoint, and activates HIFs to cause autocrine vascular endothelial growth factor (VEGF) signaling that triggers the EMT program.

Enrollment: 15 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• U.S. Veteran
• Barrett's Esophagus

Exclusion criteria

• Inability to provide informed consent
• Pregnancy or breastfeeding
• Esophageal varices
• Warfarin use
• Coagulopathy that precludes safe biopsy of the esophagus
• Comorbidity that precludes safe participation in the study

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Barrett's esophagus patients

Experimental group

Description:

Patients with Barrett's Esophagus will be enrolled. The intervention is cessation of acid-suppressing medications. Biopsies will be taken during endoscopy at Day 0, 7, and 14.

Treatment:

Other: Cessation of Acid Suppressing Medications