Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
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ClinicalTrials.gov Identifier: NCT01465113 |
Recruitment Status :
Completed
First Posted : November 4, 2011
Last Update Posted : March 10, 2016
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Short Segment Barrett's Esophagus Long Segment Barrett's Esophagus | Drug: Omeprazole Drug: Vitamin D3 Procedure: upper endoscopy Drug: Metformin | Early Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 26 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Prevention |
Official Title: | Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus |
Study Start Date : | May 2010 |
Actual Primary Completion Date : | February 2016 |
Actual Study Completion Date : | February 2016 |
Arm | Intervention/treatment |
---|---|
Experimental: Indefinite, LGD or no dysplasia arm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
|
Drug: 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). 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.
Other Name: Cholecalciferol Procedure: 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. |
Experimental: high grade dysplasia
Barrett's esophagus with high grade dysplasia
|
Drug: 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). 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.
Other Name: Cholecalciferol Procedure: 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. |
Experimental: Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
|
Drug: 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). 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.
Other Name: Cholecalciferol Procedure: 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. Drug: Metformin 500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week |
- Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression [ Time Frame: 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 [ Time Frame: 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
- decreased prostaglandin E2 expression in Barrett's esophagus [ Time Frame: 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 cyclooxygenase-2 expression [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: after 2 or 12 weeks of vitamin D supplement ]To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts 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 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01465113
United States, Ohio | |
University Hospitals Ahuja Medical Center | |
Beachwood, Ohio, United States, 44122 | |
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | |
Cleveland, Ohio, United States, 44106 | |
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | |
Cleveland, Ohio, United States, 44195 |
Principal Investigator: | Linda Cummings, MD | Case Comprehensive Cancer Center |
Responsible Party: | Case Comprehensive Cancer Center |
ClinicalTrials.gov Identifier: | NCT01465113 |
Other Study ID Numbers: |
CASE12209 |
First Posted: | November 4, 2011 Key Record Dates |
Last Update Posted: | March 10, 2016 |
Last Verified: | March 2016 |
Barrett's Esophagus Vitamin D3 cholecalciferol 15-Prostaglandin Dehydrogenase Expression metformin |
Barrett Esophagus Precancerous Conditions Neoplasms Esophageal Diseases Gastrointestinal Diseases Digestive System Diseases Vitamin D Ergocalciferols Cholecalciferol Vitamins Metformin Omeprazole |
Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Hypoglycemic Agents Bone Density Conservation Agents Calcium-Regulating Hormones and Agents Anti-Ulcer Agents Gastrointestinal Agents Proton Pump Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |