Long Segment Barrett's Esophagus, Short Segment Barrett's Esophagus
Conditions
Keywords
Barrett's Esophagus, Vitamin D3, cholecalciferol, 15-Prostaglandin Dehydrogenase Expression, metformin
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.
Interventions
DRUGOmeprazole
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).
DRUGVitamin 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.
PROCEDUREupper 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.
DRUGMetformin
500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 The following additional inclusion criteria apply for patients in the Vitamin D/metformin sub-arm of the low grade dysplasia/no dysplasia arm: * 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 The following additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression | after 12 weeks of vitamin D supplement | To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus |
| Arm 2 (high grade dysplasia): 15-Prostaglandin dehydrogenase expression | after 2 weeks of vitamin D supplement | To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry | after 2 or 12 weeks after vitamin D supplement | To determine whether 15-Prostaglandin dehydrogenase expression in Barrett's esophagus differs between RT-PCR and immunohistochemistry |
| effects on levels of Ki-67 | after 2 or 12 weeks after vitamin D supplement | To determine whether vitamin D supplementation affects levels of Ki-67, a marker for proliferation, in Barrett's esophagus |
| decreased prostaglandin E2 expression in Barrett's esophagus | after 2 or 12 weeks of vitamin D supplement | To determine whether vitamin D supplementation leads to decreased prostaglandin E2 expression in Barrett's esophagus |
| effects on insulin resistance | after 2 or 12 weeks of vitamin D supplement | To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus |
| effects on levels of caspase | after 2 or 12 weeks of vitamin D supplement | To determine whether vitamin D supplementation affects levels of caspase, a marker for apoptosis, in Barrett's esophagus |
| effects on cyclooxygenase-2 expression | after 2 or 12 weeks after vitamin D supplement | To determine whether vitamin D supplementation affects cyclooxygenase-2 expression in Barrett's esophagus |
Countries
United States
Outcome results
None listed