NCT02579460

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Dallas VA Medical Center · Federal
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Barrett's Esophagus
• Gastroesophageal Reflux Disease

Interventions

Type	Name	Description
OTHER	Cessation of Acid Suppressing Medications	Acid suppressing medications are stopped for all participants the day after baseline assessment. Subsequent evaluations are performed while the participant is not on acid-suppressing medications. Endoscopy with biopsies will be performed in all patients on day 0, 7, and 14.

Timeline

• Start date: 2015-11-01
• Primary completion: 2017-11-01
• Completion: 2017-11-01
• First posted: 2015-10-19
• Last updated: 2023-09-11

Locations

1 site across 1 country: United States