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

This study has been terminated.
(Expected recruitment numbers have not been achieved.)
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Jeffrey H Peters, University of Rochester
ClinicalTrials.gov Identifier:
NCT00624546
First received: December 28, 2007
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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 Intervention
GERD
Gastroesophageal Reflux
Drug: Prevacid Solutabs
Procedure: Antireflux surgery

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • gene expression [ Time Frame: before and after treatment ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Esophageal mucosal biopsies


Enrollment: 24
Study Start Date: January 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
gerd patients
Drug: Prevacid Solutabs
BID Prevacid Solutabs
Other Name: Prevacid solutabs
Procedure: Antireflux surgery
Lap Nissen
2
non gerd controls

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624546

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

No publications provided

Responsible Party: Jeffrey H Peters, Professor and Chair of the Department of Surgery, University of Rochester
ClinicalTrials.gov Identifier: NCT00624546     History of Changes
Other Study ID Numbers: RSRB18199, rsrb18199
Study First Received: December 28, 2007
Last Updated: January 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
GERD
gastroesophageal reflux
antireflux surgery
Barrett's
Esophagus
Esophagitis

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Lansoprazole
Dexlansoprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014