NCT02579460

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 14, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

October 19, 2015

Completed
13 days until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
Last Updated

September 11, 2023

Status Verified

September 1, 2023

Enrollment Period

2 years

First QC Date

October 14, 2015

Last Update Submit

September 7, 2023

Conditions

Barrett's EsophagusGastroesophageal Reflux Disease

Keywords

Barrett's esophagusGastroesophageal Reflux Disease

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (9)

  • change in p38 pathway from baseline to 14 days

    day 0, day 7, and day 14

  • change in phosoho-p38 from baseline to 14 days

    day 0, day 7, and day 14

  • Show oxidative DNA damage associated with p38 activation

    day 0, day 7, and day 14

  • change in VEGF from baseline to 14 days

    day 0, day 7, and day 14

  • change in APE-1 from baseline to 14 days

    day 0, day 7, and day 14

  • +4 more secondary outcomes

Study Arms (1)

Barrett's esophagus patients

EXPERIMENTAL

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.

Other: Cessation of Acid Suppressing Medications

Interventions

Cessation of Acid Suppressing MedicationsOTHER

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.

Barrett's esophagus patients

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • U.S. Veteran
  • Barrett's Esophagus

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dallas VA Medical Center

Dallas, Texas, 75216, United States

Location

Related Publications (1)

  • Zhang Q, Dunbar KB, Odze RD, Agoston AT, Wang X, Su T, Nguyen AD, Zhang X, Spechler SJ, Souza RF. Hypoxia-inducible factor-1alpha mediates reflux-induced epithelial-mesenchymal plasticity in Barrett's oesophagus patients. Gut. 2024 Jul 11;73(8):1269-1279. doi: 10.1136/gutjnl-2023-331467.

    PMID: 38641363DERIVED

MeSH Terms

Conditions

Barrett EsophagusGastroesophageal Reflux

Condition Hierarchy (Ancestors)

Precancerous ConditionsNeoplasmsEsophageal DiseasesGastrointestinal DiseasesDigestive System DiseasesEsophageal Motility DisordersDeglutition Disorders

Study Officials

  • Stuart J Spechler, MD

    Dallas VA Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

October 14, 2015

First Posted

October 19, 2015

Study Start

November 1, 2015

Primary Completion

November 1, 2017

Study Completion

November 1, 2017

Last Updated

September 11, 2023

Record last verified: 2023-09

Locations

US(1)