Effect of Antireflux Therapy on the Expression of Genes in Patients With GERD

October 23, 2015 updated by: Jeffrey H Peters, University of Rochester

Effect of Antireflux Therapy on the Expression of Genes Known to be Important in Inflammation, Metaplasia and Neoplasia in Patients With GERD

Although the symptomatic and epithelial (histologic and endoscopic) response to antireflux therapy are well known and extensively studied, little is known of the genetic events occurring in response to proton pump inhibitor therapy. Preliminary data from our laboratory has shown, for example, that COX-2 expression is not only elevated in patients with gastroesophageal reflux disease but also can be correlated with pathologic esophageal acid exposure on 24 hour pH monitoring. Similar studies have suggested that antireflux surgery may normalize COX-2 gene expression. In contrast studies following ablation of dysplastic Barrett's epithelium have shown persistence of genetic changes associated with altered cellular function, despite the return of the histologic appearance to normal. Several key mediators of inflammation, metaplasia (Barrett's) and neoplasia have now been well characterized and shown to be important factors in the pathogenesis of esophageal injury. It is likely that successful antireflux therapy returns altered expression of these mediators toward normal although this hypothesis remains largely unexplored. The aim of this study is to investigate gene expression of key mediators of the spectrum of esophageal mucosal injury and the response to antireflux therapy.

Hypothesis: Antireflux therapy (proton pump inhibitor and surgical fundoplication) normalizes the expression of genes known to be involved in the pathogenesis of inflammation (esophagitis), metaplasia (Barrett esophagus) and neoplasia (adenocarcinoma).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Aims: To determine the effects of antireflux therapy (pump inhibitor and surgical fundoplication) on gene expression of:

  1. inflammation: IL-8, IFN-g, TNF-a.
  2. intestinal metaplasia: CDX-1/2, MUC2 and Sonic hedgehog.
  3. Neoplasia: Cox-2, VEGF, and EGFR.

Study Type

Observational

Enrollment (Actual)

24

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14564
        • Strong Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects: (a) 20 patients with GERD and (b) 20 non-GERD controls.

Description

Inclusion Criteria:

For patients with GERD

  • Patients referred for anti-reflux surgery
  • On PPI therapy for at least 6 months
  • Positive ambulatory pH monitoring (%time pH<4 > 4.7)
  • Age greater than 18 years old.
  • Both genders

For non-GERD controls

  • Negative ambulatory pH monitoring OR
  • Upper endoscopy performed for non-GERD symptoms.
  • Age greater than 18 years old.
  • Both genders

Exclusion Criteria:

  • Prior foregut surgery
  • Contra-indications for operation (poor clinical status, etc.)
  • Contra-indications for endoscopy and biopsy (esophageal or gastric varices, therapeutic anticoagulation with Coumadin or Heparin, etc.)
  • Unwillingness to participate in all of the follow-up studies
  • Pregnancy
  • Patients using medications that may interfere with PPIs pharmacokinetics (sucralfate, ketoconazole (Nizoral), ampicillin (Omnipen, Principen), digoxin (Lanoxin, Lanoxicaps), and iron (Feosol, Mol-Iron, Fergon, Femiron).
  • Patients using medications that may interfere with gene expression (Immunosuppressants, Aspirin, NSAIDs, Corticosteroids).
  • Patients with diseases that may interfere with gene expression (autoimmune diseases, diseases that course with immunosuppression).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
gerd patients
Drug: Prevacid Solutabs
BID Prevacid Solutabs
Procedure: Antireflux surgery
Lap Nissen
2
non gerd controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
gene expression
Time Frame: before and after treatment
before and after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Collaborators

Takeda Pharmaceuticals North America, Inc.

Investigators

  • Principal Investigator: Jeffrey H Peters, University of Rochester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

December 28, 2007

First Submitted That Met QC Criteria

February 26, 2008

First Posted (Estimate)

February 27, 2008

Study Record Updates

Last Update Posted (Estimate)

October 26, 2015

Last Update Submitted That Met QC Criteria

October 23, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • rsrb18199

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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