Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
- Conditions
- Short Segment Barrett's EsophagusLong Segment Barrett's Esophagus
- Interventions
- Registration Number
- NCT01465113
- Lead Sponsor
- Case Comprehensive Cancer Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- 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)
- 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 exclusion criteria apply for patients in the Vitamin D/metformin sub-arm of the no dysplasia/low grade dysplasia arm:
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Indefinite, LGD or no dysplasia arm Omeprazole Barrett's esophagus patients who have no dysplasia or low grade dysplasia Indefinite, LGD or no dysplasia arm Vitamin D3 Barrett's esophagus patients who have no dysplasia or low grade dysplasia Indefinite, LGD or no dysplasia arm upper endoscopy Barrett's esophagus patients who have no dysplasia or low grade dysplasia high grade dysplasia upper endoscopy Barrett's esophagus with high grade dysplasia Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm Omeprazole Barrett's esophagus patients who have no dysplasia or low grade dysplasia Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm Vitamin D3 Barrett's esophagus patients who have no dysplasia or low grade dysplasia Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm Metformin Barrett's esophagus patients who have no dysplasia or low grade dysplasia Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm upper endoscopy Barrett's esophagus patients who have no dysplasia or low grade dysplasia high grade dysplasia Omeprazole Barrett's esophagus with high grade dysplasia high grade dysplasia Vitamin D3 Barrett's esophagus with high grade dysplasia
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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 insulin resistance after 2 or 12 weeks of vitamin D supplement To determine whether vitamin D supplementation affects insulin resistance 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
Trial Locations
- Locations (3)
University Hospitals Ahuja Medical Center
🇺🇸Beachwood, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States