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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
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Study Description
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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.

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

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.

Study Design
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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

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


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
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Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01465113     History of Changes
Other Study ID Numbers: CASE12209
First Posted: November 4, 2011    Key Record Dates
Last Update Posted: March 10, 2016
Last Verified: March 2016

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