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OpenTrials
Completed

NCT Number: NCT02579460

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

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.

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Key information

Conditions

Barrett's Esophagus Barrett Esophagus Deglutition Disorders Digestive System Diseases Esophageal Diseases Esophageal Motility Disorders Gastroesophageal Reflux Gastroesophageal Reflux Disease Gastrointestinal Diseases Neoplasms Precancerous Conditions

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Dallas VA Medical Center

Dallas, Texas, 75216, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cessation of Acid Suppressing Medications

Other

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.

Primary outcomes

  1. Change in esophageal mucosal inflammation using histopathological assessment from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    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.

Secondary outcomes

  1. change in p38 pathway from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    p38 and components of the p38 pathway will be measured in the esophageal mucosa at baseline, 7 days, and at 14 days

  2. change in phosoho-p38 from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    phospho-p38 will be measured in the esophageal mucosa at baseline, day 7, and at day 14

  3. Show oxidative DNA damage associated with p38 activation

    Time frame: day 0, day 7, and day 14

    OxiSelect Oxidative DNA Damage ELISA assay of Barrett's mucosa at baseline, day 7, and day 14

  4. change in VEGF from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    VEGF will be measured in the esophageal mucosa at baseline, 7 days, and at day 14

  5. change in APE-1 from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    APE-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14

  6. change in NPM1 from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    NPM-1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14

  7. change in phospho-NPM1 from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    phospho-NPM1 will be measured in the esophageal mucosa at baseline, day 7, and at day 14

  8. change in miRNA expression from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    miRNAs will be measured in the esophageal mucosa and in exosomes isolated from the blood at baseline, day 7, and day 14

  9. change in HIF expression from baseline to 14 days

    Time frame: day 0, day 7, and day 14

    HIF expression will be measured in the esophageal mucosa at baseline, day 7, and day 14

Sponsors and collaborators

Lead sponsor

Dallas VA Medical Center

Fed

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Oct 19, 2015
Registry last updated
Sep 11, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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