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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00624546
Recruitment Status : Terminated (Expected recruitment numbers have not been achieved.)
First Posted : February 27, 2008
Last Update Posted : October 26, 2015
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Jeffrey H Peters, University of Rochester

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).

Condition or disease Intervention/treatment
GERD Gastroesophageal Reflux Drug: Prevacid Solutabs Procedure: Antireflux surgery

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.

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Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Cohort
Time Perspective: Prospective
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 Start Date : January 2009
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
gerd patients
Drug: Prevacid Solutabs
BID Prevacid Solutabs

Procedure: Antireflux surgery
Lap Nissen

non gerd controls

Primary Outcome Measures :
  1. gene expression [ Time Frame: before and after treatment ]

Biospecimen Retention:   Samples With DNA
Esophageal mucosal biopsies

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects: (a) 20 patients with GERD and (b) 20 non-GERD controls.

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00624546

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United States, New York
Strong Memorial Hospital
Rochester, New York, United States, 14564
Sponsors and Collaborators
University of Rochester
Takeda Pharmaceuticals North America, Inc.
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Principal Investigator: Jeffrey H Peters University of Rochester

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Responsible Party: Jeffrey H Peters, Professor and Chair of the Department of Surgery, University of Rochester Identifier: NCT00624546     History of Changes
Other Study ID Numbers: RSRB18199
First Posted: February 27, 2008    Key Record Dates
Last Update Posted: October 26, 2015
Last Verified: October 2015

Keywords provided by Jeffrey H Peters, University of Rochester:
gastroesophageal reflux
antireflux surgery

Additional relevant MeSH terms:
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Gastroesophageal Reflux
Esophagitis, Peptic
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Peptic Ulcer
Duodenal Diseases
Intestinal Diseases
Stomach Diseases
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action