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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01093755
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 56
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammation; Barrett's Esophagus	Drug: dexlansoprazole; Drug: Omeprazole	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett's Esophagus Following Ablation?: A Randomized Controlled Trial
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Prasad Iyer, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prasad G. Iyer, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01093755
• Other Study ID Numbers: 09-007252
• First Posted: Mar 26, 2010
• Last Update Posted: Mar 17, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Prasad G. Iyer, MD, Mayo Clinic: Barrett's Esophagus; Radiofrequency ablation; Patients post-radiofrequency ablation for Barrett's Esophagus.
• Additional relevant MeSH terms: Barrett Esophagus; Esophagitis; Inflammation; Omeprazole; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants were recruited from Mayo Clinic patients in Rochester, Minnesota who had undergone an ablation procedure for Barrett's Esophagus.

Arm/Group Title	Dexlansoprazole	Omeprazole
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	16	14
COMPLETED	13	10
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Dexlansoprazole	Omeprazole	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	16	14	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.9 (6.9)	59.1 (8.9)	61.5 (8.14)
Sex: Female, Male (Count of Participants)
Female	2 12.5%	2 14.3%	4 13.3%
Male	14 87.5%	12 85.7%	26 86.7%
Region of Enrollment (participants) [Number]
United States	16 100%	14 100%	30 100%
High Grade Dysplasia/Intramucosal Carcinoma (participants) [Number]
Subjects with High-Grade Dysplasia/Carcinoma	12 75%	10 71.4%	22 73.3%
Subjects with Low-Grade Dysplasia	4 25%	4 28.6%	8 26.7%
Body Mass Index (kg/height in meters^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/height in meters^2]	30.9 (3.4)	29.3 (4.2)	30.14 (3.84)
Barrett's Esophagus segment length, pre-ablation (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	5.3 (3.5)	4.8 (4.3)	5.06 (3.84)
Diaphragmatic Hernia present (Number) [Number]
Subjects with Diaphragmatic Hernia	15 93.8%	13 92.9%	28 93.3%
Subjects without Diaphragmatic Hernia	1 6.3%	1 7.1%	2 6.7%
Diaphragmatic Hernia length (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	3.6 (2.3)	3.0 (1.7)	3.3 (2.05)
Number undergoing Endoscopic Mucosal Resection (Number) [Number]
Subjects undergoing resection	16 100%	12 85.7%	28 93.3%
Subjects not undergoing resection	0 0%	2 14.3%	2 6.7%

Outcome Measures

1. Primary Outcome

Title	Change in Inflammation Biomarker Tissue PGE2 Level
Description	Change from baseline in esophageal tissue biopsy prostaglandin E2 (PGE2) level, as determined by enzyme immunoassay
Time Frame	3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexlansoprazole	Omeprazole
Arm/Group Description	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	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
Measure Participants	16	14
Change from baseline at 3 months	1.35 (3.16)	-0.02 (1.47)
Change from baseline at 6 months	1.19 (3.58)	-0.06 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole, Omeprazole
	Comments	Comparison between the two treatment groups at 3 months
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole, Omeprazole
	Comments	Comparison between the two treatment groups at 6 months
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Change in Esophageal Inflammation Biomarker COX-2 Gene Expression
Description	Change from baseline in esophageal issue biopsy cyclooxygenase-2 (COX-2) gene expression, as determined by Western blot.
Time Frame	3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexlansoprazole	Omeprazole
Arm/Group Description	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	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
Measure Participants	16	14
Change from baseline at 3 months	36.81 (73.55)	27.17 (176.82)
Change from baseline at 6 months	56.54 (98.77)	25.49 (210.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole, Omeprazole
	Comments	Comparison between the two treatment groups at 3 months
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole
	Comments	Comparison between the two treatment groups at 6 months
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Baseline to 6 months
Arm/Group Title	Dexlansoprazole		Omeprazole
Arm/Group Description	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		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
All Cause Mortality
	Dexlansoprazole		Omeprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexlansoprazole		Omeprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Dexlansoprazole		Omeprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.