Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett's Esophagus Following Ablation?

Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett's Esophagus Following Ablation?: A Randomized Controlled Trial

The investigators hypothesize that intensive acid suppression with a long acting high potency proton pump inhibitor (PPI) drug dexlansoprazole will lead to a greater decrease in levels of inflammatory mediators (compared to conventional PPIs) in the esophagus, which could potentially lead to decreased recurrence of intestinal metaplasia following endoscopic ablation.

Study Overview

• Status: Completed
• Conditions: Inflammation; Barrett's Esophagus
• Intervention / Treatment: Drug: dexlansoprazole; Drug: Omeprazole

Detailed Description

Patients who achieve complete remission of intestinal metaplasia following ablation will be randomized (using concealed allocation, like the flip of a coin) to either intensive acid suppression with dexlansoprazole 60-90 mg/day or to symptom guided acid suppression with escalating doses of omeprazole (20-60 mg/day) for 6 months. Control of reflux will be assessed using 24 hour ambulatory pH monitoring. The need to escalate drug dosage at the 3 month visit will be determined by presence of excessive acid exposure on ambulatory pH monitoring. Biopsies of esophageal tissue will be obtained at baseline, then at 3 months and 6 months following randomization to measure changes in inflammatory biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients who have undergone ablation for Barrett's Esophagus (BE) and High Grade Dysplasia (HGD) or Low Grade Dysplasia (LGD) with Photodynamic Therapy (PDT)/Radiofrequency ablation and endoscopic mucosal resection who have no endoscopic and histologic evidence of specialized intestinal metaplasia on biopsies from the esophagus on two successive endoscopies post ablation will be offered enrollment in the study.

Inclusion criteria:

1. Absence of intestinal metaplasia on endoscopy (under Narrow Band Imaging) and on histology (from biopsies taken from gastroesophageal junction and distal esophagus) on two successive surveillance endoscopies.
2. Able to consent to study
3. Males and females age 18-90
4. Life expectancy of 5 years or greater.

Exclusion criteria:

1. Pregnancy
2. Inability to consent for the procedure
3. Anticoagulation therapy precluding performance of ambulatory pH monitoring and/or biopsies
4. Intolerance to proton pump inhibitors
5. Elevation in Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), (liver enzymes), bilirubin or alkaline phosphatase more than five times the upper limit of normal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dexlansoprazole; Participants will be treated with dexlansoprazole 60-90 mg/day for 6 months	Drug: dexlansoprazole; Intensive acid suppression with dexlansoprazole 60-90 mg/day for 6 months; Other Names: Dexilant
Active Comparator: omeprazole; Participants will be treated with omeprazole 20mg/day for a minimum of 6 weeks. If symptomatic can increase dose by 20mg twice.	Drug: Omeprazole; Escalating doses of omeprazole (20-60 mg/day) for 6 months; Other Names: Prilosec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Inflammation Biomarker Tissue PGE2 Level	Change from baseline in esophageal tissue biopsy prostaglandin E2 (PGE2) level, as determined by enzyme immunoassay	3 months, 6 months
Change in Esophageal Inflammation Biomarker COX-2 Gene Expression	Change from baseline in esophageal issue biopsy cyclooxygenase-2 (COX-2) gene expression, as determined by Western blot.	3 months, 6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Prasad Iyer, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 24, 2010
• First Submitted That Met QC Criteria: March 25, 2010
• First Posted (Estimate): March 26, 2010

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Barrett's Esophagus; Radiofrequency ablation; Patients post-radiofrequency ablation for Barrett's Esophagus.
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Esophageal Diseases; Precancerous Conditions; Inflammation; Barrett Esophagus; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole; Omeprazole
• Other Study ID Numbers: 09-007252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No