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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02579460
Other study ID # 15-022
Secondary ID 1R01DK103598-01A
Status Completed
Phase N/A
First received
Last updated
Start date November 2015
Est. completion date November 2017

Study information

Verified date September 2023
Source Dallas VA Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date November 2017
Est. primary completion date November 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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

Study Design


Intervention

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.

Locations

Country Name City State
United States Dallas VA Medical Center Dallas Texas

Sponsors (2)

Lead Sponsor Collaborator
Dallas VA Medical Center National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days Inflammation of the esophageal mucosa will be measured at baseline, 7 days, and at 14 days. Esophageal mucosal inflammation will be measured using esophageal mucosal biopsy specimens, and histopatholgical grading. Mucosal infiltration with inflammatory cells (neutrophils, eosinophils, and lymphocytes) will be measured. day 0, day 7, and day 14
Secondary change in p38 pathway from baseline to 14 days p38 and components of the p38 pathway will be measured in the esophageal mucosa at baseline, 7 days, and at 14 days day 0, day 7, and day 14
Secondary change in phosoho-p38 from baseline to 14 days phospho-p38 will be measured in the esophageal mucosa at baseline, day 7, and at day 14 day 0, day 7, and day 14
Secondary Show oxidative DNA damage associated with p38 activation OxiSelect Oxidative DNA Damage ELISA assay of Barrett's mucosa at baseline, day 7, and day 14 day 0, day 7, and day 14
Secondary change in VEGF from baseline to 14 days VEGF will be measured in the esophageal mucosa at baseline, 7 days, and at day 14 day 0, day 7, and day 14
Secondary change in APE-1 from baseline to 14 days APE-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14 day 0, day 7, and day 14
Secondary change in NPM1 from baseline to 14 days NPM-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14 day 0, day 7, and day 14
Secondary change in phospho-NPM1 from baseline to 14 days phospho-NPM1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14 day 0, day 7, and day 14
Secondary change in miRNA expression from baseline to 14 days miRNAs will be measured in the esophageal mucosa and in exosomes isolated from the blood at baseline, day 7, and day 14 day 0, day 7, and day 14
Secondary change in HIF expression from baseline to 14 days HIF expression will be measured in the esophageal mucosa at baseline, day 7, and day 14 day 0, day 7, and day 14
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