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

Primary Purpose

Short Segment Barrett's Esophagus, Long Segment Barrett's Esophagus

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Omeprazole
Vitamin D3
Vitamin D3
upper endoscopy
Metformin
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Short Segment Barrett's Esophagus focused on measuring Barrett's Esophagus, Vitamin D3, cholecalciferol, 15-Prostaglandin Dehydrogenase Expression, metformin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospitals Ahuja Medical Center
  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Indefinite, LGD or no dysplasia arm

high grade dysplasia

Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm

Arm Description

Barrett's esophagus patients who have no dysplasia or low grade dysplasia

Barrett's esophagus with high grade dysplasia

Barrett's esophagus patients who have no dysplasia or low grade dysplasia

Outcomes

Primary Outcome Measures

Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
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
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
To determine whether vitamin D supplementation leads to decreased prostaglandin E2 expression in Barrett's esophagus
effects on cyclooxygenase-2 expression
To determine whether vitamin D supplementation affects cyclooxygenase-2 expression in Barrett's esophagus
15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry
To determine whether 15-Prostaglandin dehydrogenase expression in Barrett's esophagus differs between RT-PCR and immunohistochemistry
effects on levels of Ki-67
To determine whether vitamin D supplementation affects levels of Ki-67, a marker for proliferation, in Barrett's esophagus
effects on levels of caspase
To determine whether vitamin D supplementation affects levels of caspase, a marker for apoptosis, in Barrett's esophagus
effects on insulin resistance
To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus

Full Information

First Posted
November 1, 2011
Last Updated
March 9, 2016
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01465113
Brief Title
Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
Official Title
Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Short Segment Barrett's Esophagus, Long Segment Barrett's Esophagus
Keywords
Barrett's Esophagus, Vitamin D3, cholecalciferol, 15-Prostaglandin Dehydrogenase Expression, metformin

7. Study Design

Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Indefinite, LGD or no dysplasia arm
Arm Type
Experimental
Arm Description
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
Arm Title
high grade dysplasia
Arm Type
Experimental
Arm Description
Barrett's esophagus with high grade dysplasia
Arm Title
Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Arm Type
Experimental
Arm Description
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention 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).
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Cholecalciferol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Cholecalciferol
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
upper endoscopy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
500mg for the first week, 1000mg during the second week, 1500mg during the third week, maximum dose of 2000mg in the fourth week
Primary Outcome Measure Information:
Title
Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
Description
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
Time Frame
after 12 weeks of vitamin D supplement
Title
Arm 2 (high grade dysplasia): 15-Prostaglandin dehydrogenase expression
Description
To determine whether vitamin D supplementation induces 15-Prostaglandin dehydrogenase expression as measured by RT-PCR in Barrett's esophagus
Time Frame
after 2 weeks of vitamin D supplement
Secondary Outcome Measure Information:
Title
decreased prostaglandin E2 expression in Barrett's esophagus
Description
To determine whether vitamin D supplementation leads to decreased prostaglandin E2 expression in Barrett's esophagus
Time Frame
after 2 or 12 weeks of vitamin D supplement
Title
effects on cyclooxygenase-2 expression
Description
To determine whether vitamin D supplementation affects cyclooxygenase-2 expression in Barrett's esophagus
Time Frame
after 2 or 12 weeks after vitamin D supplement
Title
15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry
Description
To determine whether 15-Prostaglandin dehydrogenase expression in Barrett's esophagus differs between RT-PCR and immunohistochemistry
Time Frame
after 2 or 12 weeks after vitamin D supplement
Title
effects on levels of Ki-67
Description
To determine whether vitamin D supplementation affects levels of Ki-67, a marker for proliferation, in Barrett's esophagus
Time Frame
after 2 or 12 weeks after vitamin D supplement
Title
effects on levels of caspase
Description
To determine whether vitamin D supplementation affects levels of caspase, a marker for apoptosis, in Barrett's esophagus
Time Frame
after 2 or 12 weeks of vitamin D supplement
Title
effects on insulin resistance
Description
To determine whether vitamin D supplementation affects insulin resistance in Barrett's esophagus
Time Frame
after 2 or 12 weeks of vitamin D supplement

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda Cummings, MD
Organizational Affiliation
Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Ahuja Medical Center
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

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

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