Clinical trial NCT02579460: Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
Official title: Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Barrett's Esophagus
Gastroesophageal Reflux Disease
Keywords: Barrett's esophagus
Gastroesophageal Reflux Disease
Lead sponsor: Dallas VA Medical Center
Sponsor class: FED
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-10-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days
timeFrame: day 0, day 7, and day 14
Secondary outcomes:
measure: change in p38 pathway from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in phosoho-p38 from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: Show oxidative DNA damage associated with p38 activation
timeFrame: day 0, day 7, and day 14
measure: change in VEGF from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in APE-1 from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in NPM1 from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in phospho-NPM1 from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in miRNA expression from baseline to 14 days
timeFrame: day 0, day 7, and day 14
measure: change in HIF expression from baseline to 14 days
timeFrame: day 0, day 7, and day 14
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
Study officials:
affiliation: Dallas VA Medical Center
name: Stuart J Spechler, MD
role: PRINCIPAL_INVESTIGATOR
References: