Barrett's Esophagus, Inflammation
Conditions
Keywords
Barrett's Esophagus, Radiofrequency ablation, Patients post-radiofrequency ablation for Barrett's Esophagus.
Brief summary
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.
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.
Interventions
DRUGdexlansoprazole
Intensive acid suppression with dexlansoprazole 60-90 mg/day for 6 months
DRUGOmeprazole
Escalating doses of omeprazole (20-60 mg/day) for 6 months
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammation Biomarker Tissue PGE2 Level | 3 months, 6 months | Change from baseline in esophageal tissue biopsy prostaglandin E2 (PGE2) level, as determined by enzyme immunoassay |
| Change in Esophageal Inflammation Biomarker COX-2 Gene Expression | 3 months, 6 months | Change from baseline in esophageal issue biopsy cyclooxygenase-2 (COX-2) gene expression, as determined by Western blot. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Mayo Clinic patients in Rochester, Minnesota who had undergone an ablation procedure for Barrett's Esophagus.
Participants by arm
| Arm | Count |
|---|---|
| Dexlansoprazole Participants will be treated with dexlansoprazole 60-90 mg/day for 6 months
dexlansoprazole: Intensive acid suppression with dexlansoprazole 60-90 mg/day for 6 months | 16 |
| Omeprazole Participants will be treated with omeprazole 20mg/day for a minimum of 6 weeks. If symptomatic can increase dose by 20mg twice.
Omeprazole: Escalating doses of omeprazole (20-60 mg/day) for 6 months | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Dexlansoprazole | Omeprazole | Total |
|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 6.9 | 59.1 Years STANDARD_DEVIATION 8.9 | 61.5 Years STANDARD_DEVIATION 8.14 |
| Barrett's Esophagus segment length, pre-ablation | 5.3 cm STANDARD_DEVIATION 3.5 | 4.8 cm STANDARD_DEVIATION 4.3 | 5.06 cm STANDARD_DEVIATION 3.84 |
| Body Mass Index | 30.9 kg/height in meters^2 STANDARD_DEVIATION 3.4 | 29.3 kg/height in meters^2 STANDARD_DEVIATION 4.2 | 30.14 kg/height in meters^2 STANDARD_DEVIATION 3.84 |
| Diaphragmatic Hernia length | 3.6 cm STANDARD_DEVIATION 2.3 | 3.0 cm STANDARD_DEVIATION 1.7 | 3.3 cm STANDARD_DEVIATION 2.05 |
| Diaphragmatic Hernia present Subjects with Diaphragmatic Hernia | 15 Participants | 13 Participants | 28 Participants |
| Diaphragmatic Hernia present Subjects without Diaphragmatic Hernia | 1 Participants | 1 Participants | 2 Participants |
| High Grade Dysplasia/Intramucosal Carcinoma Subjects with High-Grade Dysplasia/Carcinoma | 12 participants | 10 participants | 22 participants |
| High Grade Dysplasia/Intramucosal Carcinoma Subjects with Low-Grade Dysplasia | 4 participants | 4 participants | 8 participants |
| Number undergoing Endoscopic Mucosal Resection Subjects not undergoing resection | 0 Participants | 2 Participants | 2 Participants |
| Number undergoing Endoscopic Mucosal Resection Subjects undergoing resection | 16 Participants | 12 Participants | 28 Participants |
| Region of Enrollment United States | 16 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
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.
Time frame: 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexlansoprazole | Change in Esophageal Inflammation Biomarker COX-2 Gene Expression | Change from baseline at 6 months | 56.54 % of tubulin | Standard Deviation 98.77 |
| Dexlansoprazole | Change in Esophageal Inflammation Biomarker COX-2 Gene Expression | Change from baseline at 3 months | 36.81 % of tubulin | Standard Deviation 73.55 |
| Omeprazole | Change in Esophageal Inflammation Biomarker COX-2 Gene Expression | Change from baseline at 3 months | 27.17 % of tubulin | Standard Deviation 176.82 |
| Omeprazole | Change in Esophageal Inflammation Biomarker COX-2 Gene Expression | Change from baseline at 6 months | 25.49 % of tubulin | Standard Deviation 210.67 |
Comparison: Comparison between the two treatment groups at 3 monthsp-value: 0.7Wilcoxon (Mann-Whitney)
Comparison: Comparison between the two treatment groups at 6 monthsp-value: 0.64Wilcoxon (Mann-Whitney)
Primary
Change in Inflammation Biomarker Tissue PGE2 Level
Change from baseline in esophageal tissue biopsy prostaglandin E2 (PGE2) level, as determined by enzyme immunoassay
Time frame: 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexlansoprazole | Change in Inflammation Biomarker Tissue PGE2 Level | Change from baseline at 3 months | 1.35 nanograms/gram of tissue | Standard Deviation 3.16 |
| Dexlansoprazole | Change in Inflammation Biomarker Tissue PGE2 Level | Change from baseline at 6 months | 1.19 nanograms/gram of tissue | Standard Deviation 3.58 |
| Omeprazole | Change in Inflammation Biomarker Tissue PGE2 Level | Change from baseline at 3 months | -0.02 nanograms/gram of tissue | Standard Deviation 1.47 |
| Omeprazole | Change in Inflammation Biomarker Tissue PGE2 Level | Change from baseline at 6 months | -0.06 nanograms/gram of tissue | Standard Deviation 1.45 |
Comparison: Comparison between the two treatment groups at 3 monthsp-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Comparison between the two treatment groups at 6 monthsp-value: 0.52Wilcoxon (Mann-Whitney)