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

Gastroesophageal Reflux Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00624546
• Other study ID #: RSRB18199
• Secondary ID: rsrb18199
• Status: Terminated
• Phase: N/A
• First received: December 28, 2007
• Last updated: October 23, 2015
• Start date: January 2009
• Est. completion date: January 2014

Study information

• Verified date: October 2015
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• GERD

Intervention

Drug:
• Prevacid Solutabs
BID Prevacid Solutabs

Procedure:
• Antireflux surgery
Lap Nissen

Locations

Country	Name	City	State
United States	Strong Memorial Hospital	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester	Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	gene expression		before and after treatment	No