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

Purpose

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.

Condition	Intervention	Phase
Short Segment Barrett's Esophagus Long Segment Barrett's Esophagus	Drug: Omeprazole Drug: Vitamin D3 Procedure: upper endoscopy Drug: Metformin	Phase 0


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus

Resource links provided by NLM:

MedlinePlus related topics: Endoscopy Vitamin D

Drug Information available for: Cholecalciferol Metformin Metformin hydrochloride Vitamin D Omeprazole Omeprazole magnesium

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression [ Time Frame: after 12 weeks of vitamin D supplement ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus

Secondary Outcome Measures:

decreased prostaglandin E2 expression in Barrett's esophagus [ Time Frame: after 2 or 12 weeks of vitamin D supplement ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus


Enrollment:	26
Study Start Date:	May 2010
Study Completion Date:	February 2016
Primary Completion Date:	February 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465113

Locations


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

Sponsors and Collaborators

Case Comprehensive Cancer Center

Investigators


Principal Investigator:	Linda Cummings, MD	Case Comprehensive Cancer Center

More Information


Responsible Party:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01465113 History of Changes
Other Study ID Numbers:	CASE12209
Study First Received:	November 1, 2011
Last Updated:	March 9, 2016
Health Authority:	United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:


Barrett's Esophagus Vitamin D3 cholecalciferol 15-Prostaglandin Dehydrogenase Expression metformin

Additional relevant MeSH terms:


Barrett Esophagus Digestive System Abnormalities Digestive System Diseases Esophageal Diseases Gastrointestinal Diseases Vitamins Vitamin D Ergocalciferols Cholecalciferol Metformin Omeprazole	Micronutrients Growth Substances Physiological Effects of Drugs Hypoglycemic Agents Bone Density Conservation Agents Anti-Ulcer Agents Gastrointestinal Agents Proton Pump Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2016