The Frequency of Eosinophilic Esophagitis in Patients With Heartburn That is Refractory to Proton Pump Inhibitors

Background: Up to 40% of patients who are treated with PPIs for symptoms that are thought to be due to GERD experience only incomplete relief of their symptoms. Those patients are deemed "PPI failures." Esophageal pH monitoring studies have shown that PPI failure rarely is due to persistent acid reflux. Recently, heartburn that is refractory to treatment with PPIs has been described in patients with eosinophilic esophagitis, a disorder of unknown etiology in which eosinophils infiltrate the squamous epithelium of the esophagus, where they cause symptoms and tissue injury. Presently, it is not clear how often eosinophilic esophagitis underlies PPI failure for patients with GERD symptoms.

Purpose: To estimate the frequency with which eosinophilic esophagitis is the cause of "PPI failure" in patients thought to have heartburn due to GERD.

Methods: Patients referred to the Division of Gastroenterology at the Dallas VA Medical Center for the evaluation of heartburn that is refractory to PPI therapy will be invited to participate in the study. Patients who provide informed consent will have a medical history taken. Women of child bearing potential will have a pregnancy test. The patients' current PPI therapy will be discontinued, and patients will be treated with lansoprazole 30 mg BID for one week. The patient will return to the clinic one week later. Patients who feel that their heartburn has not improved by more than 50% from baseline will have an endoscopic evaluation. During the endoscopic examination, biopsy specimens will be taken as follows: A. Two specimens from the proximal esophagus at 20 cm from the incisor teeth. B. Two specimens from the mid-esophagus at 28 cm from the incisor teeth. C. Two specimens from the distal esophagus, 3 cm above the squamo-columnar junction. D. Two specimens from the distal esophagus, 1 cm above the squamo-columnar junction. E. Two specimens from the second portion of the duodenum (to see if the eosinophilia is confined to the esophagus, or part of a more extensive eosinophilic gastroenteritis). A diagnosis of eosinophilic esophagitis will be made if there is at least one high-power field with >25 eosinophils, or two or more high-power fields with >15 eosinophils.

Potential Benefits: This study will provide an estimate on the frequency with which eosinophilic esophagitis is the cause of "PPI failure" in patients thought to have heartburn due to GERD. This has substantial potential importance for patient management.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease; Eosinophilic Esophagitis
• Intervention / Treatment: Drug: Treat with lansoprazole 30 mg BID for 2 weeks, endoscopic examination with esophageal biopsy for patients with persistent symptoms

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Male and female patients ages 18 years and older who are referred to the Division of Gastroenterology at the Dallas VA Medical Center for the evaluation of heartburn that is refractory to PPI therapy

Exclusion Criteria:

1. Patients unwilling or unable to provide informed consent.
2. Allergy to lansoprazole.
3. Patients taking warfarin.
4. Coagulopathy that precludes safe biopsy of the esophagus.
5. Comorbidity that precludes safe participation in the study.
6. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Eosinophilic Esophagitis	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Who Had Resolution of Heartburn With Lansoprazole	Resolution of heartburn defined as >50% improvement in symptoms	After 8 weeks of treatment

Collaborators and Investigators

• Sponsor: Dallas VA Medical Center
• Collaborators: TAP Pharmaceutical Products Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: July 27, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 28, 2011

Study Record Updates

• Last Update Posted (Estimate): February 27, 2013
• Last Update Submitted That Met QC Criteria: February 26, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Eosinophilic esophagitis; Gastroesophageal reflux; Proton pump inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Gastroesophageal Reflux; Eosinophilic Esophagitis; Heartburn; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: VAIRB06-093