Effect of Antireflux Therapy on the Expression of Genes in Patients With GERD
Information source: University of Rochester
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: GERD; Gastroesophageal Reflux
Intervention: Prevacid Solutabs (Drug); Antireflux surgery (Procedure)
Phase: N/A
Status: Recruiting
Sponsored by: University of Rochester Official(s) and/or principal investigator(s):
Jeffrey H Peters, Principal Investigator, Affiliation: University of Rochester
Overall contact:
Jeffrey H Peters, MD, Phone: 585-275-2725, Email: jeffrey_peters@urmc.rochester.edu
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).
Clinical Details
Official title: Effect of Antireflux Therapy on the Expression of Genes Known to be Important in Inflammation, Metaplasia and Neoplasia in Patients With GERD
Study design: Cohort, Prospective
Primary outcome: gene expression
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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).
Locations and Contacts
Jeffrey H Peters, MD, Phone: 585-275-2725, Email: jeffrey_peters@urmc.rochester.edu
Strong Memorial Hospital, Rochester, New York 14564, United States; Recruiting
Jeffrey H. Peters, MD, Principal Investigator
Additional Information
Starting date: January 2009
Ending date: December 2010
Last updated: July 16, 2009
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