Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus

NCT ID: NCT01465113

Last Updated: 2016-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2016-02-29

Brief Summary

This study is being conducted to determine if vitamin D supplementation increases the level of a protein that may be involved in decreasing the risk of esophageal cancer in patients with Barrett's esophagus. Subjects with Barrett's esophagus will take vitamin D supplementation for 2-12 weeks depending on the severity of their condition, and receive an upper endoscopy procedure before and after vitamin D supplementation trial.

Detailed Description

28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor). The purpose of the run-in phase is to minimize esophagitis, which can cause histologic changes that can be confused with dysplasia. After the run-in phase, subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, research biopsies will be obtained for the study. Subjects eligible and continuing in the study will take vitamin D3 (Cholecalciferol) 50,000 IU capsules once weekly with or without daily metformin for a total of two or twelve weeks depending on the severity of Barrett's esophagus. After completion of vitamin D3 subjects will return for an EGD (endoscopy) and biopsies for the research study.

Conditions

Short Segment Barrett's Esophagus; Long Segment Barrett's Esophagus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Indefinite, LGD or no dysplasia arm

Barrett's esophagus patients who have no dysplasia or low grade dysplasia

Group Type: EXPERIMENTAL

Omeprazole

Intervention Type: DRUG

28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor).

Vitamin D3

Intervention Type: DRUG

These patients (indefinite for dysplasia, LGD, or no dysplasia) will take vitamin D3 50,000 IU once a week for 12 weeks following the upper endoscopy.

upper endoscopy

Intervention Type: PROCEDURE

After the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels.

high grade dysplasia

Barrett's esophagus with high grade dysplasia

Group Type: EXPERIMENTAL

Omeprazole

Intervention Type: DRUG

28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor).

Vitamin D3

Intervention Type: DRUG

Due to the risk of progression, subjects with Barrett's esophagus with high grade dysplasia will take vitamin D3 50,000 IU once a week for 2 weeks.

upper endoscopy

Intervention Type: PROCEDURE

After the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels.

Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm

Barrett's esophagus patients who have no dysplasia or low grade dysplasia

Group Type: EXPERIMENTAL

Omeprazole

Intervention Type: DRUG

28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor).

Vitamin D3

Intervention Type: DRUG

These patients (indefinite for dysplasia, LGD, or no dysplasia) will take vitamin D3 50,000 IU once a week for 12 weeks following the upper endoscopy.

upper endoscopy

Intervention Type: PROCEDURE

After the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels.

Metformin

Intervention Type: DRUG

500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week

Interventions

Omeprazole

28-day run-in phase during which subjects are treated with a proton pump inhibitor (omeprazole 20 mg po q day or an equivalent dose of another proton pump inhibitor).

Intervention Type: DRUG

Vitamin D3

These patients (indefinite for dysplasia, LGD, or no dysplasia) will take vitamin D3 50,000 IU once a week for 12 weeks following the upper endoscopy.

Intervention Type: DRUG

Vitamin D3

Due to the risk of progression, subjects with Barrett's esophagus with high grade dysplasia will take vitamin D3 50,000 IU once a week for 2 weeks.

Intervention Type: DRUG

upper endoscopy

After the run-in phase subjects will undergo an upper endoscopy for Barrett's surveillance or Barrett's mapping as part of routine clinical care. At the time of endoscopy, in addition to large cup forceps biopsies obtained for surveillance or mapping as part of standard care, research biopsies will be obtained for the study. Following vitamin D3 supplementation, all subjects will undergo a repeat upper endoscopy for additional large cup forceps biopsies for measurement of post-treatment mucosal levels.

Intervention Type: PROCEDURE

Metformin

500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week

Intervention Type: DRUG

Other Intervention Names

Cholecalciferol; Cholecalciferol

Eligibility Criteria

Inclusion Criteria

• Known diagnosis of short-segment or long-segment Barrett's esophagus as previously made by upper endoscopy showing salmon-colored distal esophageal mucosa and biopsies revealing intestinal metaplasia with goblet cells. Potential study subjects may be contacted by mailings or phone calls or may be approached in clinic. Additionally, potential study subjects may be approached using a web-based recruitment tool. Informed consent will be obtained by a research coordinator or study investigator.
• Subjects may be taking calcium supplements or have previous history of hypercalcemia
• Subjects may have diabetes mellitus
• Subjects may have a history of prior malignancy except for esophageal adenocarcinoma
• Willing to donate 90 mL of blood and endoscopic mucosal biopsies for research

• At least 2 cm circumferential Barrett's esophagus segment length (C2M2 by Prague C & M criteria)
• Normal renal function (defined as creatinine within normal institutional limits)

Exclusion Criteria

• Pregnancy
• Known chronic liver disease (Child's B cirrhosis)
• Known chronic kidney disease (creatinine ≥ 3.0)
• Esophageal adenocarcinoma
• Allergic reaction to omeprazole
• Allergic reaction to vitamin D
• Unable or unwilling to provide informed consent
• Known hypercalcemia
• Previous ablative therapy for Barrett's esophagus
• Patients on a stable (>/=4 week duration) dose of >2000 IU/day (or equivalent) of vitamin D supplementation

• Allergic reaction to metformin
• History of diabetes mellitus
• History of lactic acidosis
• History of B12 deficiency
• Participants may not be using metformin, cimetidine (Tagamet) furosemide (Lasix), nifedipine (Cardizem), or any other drug contraindicated for use with metformin.
• Treatment with other oral hypoglycemic agents
• Participants planning to undergo elective radiologic studies involving intravascular administration of iodinated contrast materials.
• Known chronic kidney disease with creatinine greater than normal institutional limits

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda Cummings, MD

Role: PRINCIPAL_INVESTIGATOR

Case Comprehensive Cancer Center

Locations

University Hospitals Ahuja Medical Center

Beachwood, Ohio, United States

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE12209

Identifier Type: -

Identifier Source: org_study_id