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

NCT ID: NCT00624546

Last Updated: 2015-10-26

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-01-31

Brief Summary

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).

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.

Conditions

GERD; Gastroesophageal Reflux

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

gerd patients

Prevacid Solutabs

Intervention Type: DRUG

BID Prevacid Solutabs

Antireflux surgery

Intervention Type: PROCEDURE

Lap Nissen

2

non gerd controls

No interventions assigned to this group

Interventions

Prevacid Solutabs

BID Prevacid Solutabs

Intervention Type: DRUG

Antireflux surgery

Lap Nissen

Intervention Type: PROCEDURE

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey H Peters

Professor and Chair of the Department of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey H Peters

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

Strong Memorial Hospital

Rochester, New York, United States

Countries

United States

Other Identifiers

rsrb18199

Identifier Type: -

Identifier Source: secondary_id

RSRB18199

Identifier Type: -

Identifier Source: org_study_id