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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Case Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01465113
First received: November 1, 2011
Last updated: May 28, 2014
Last verified: May 2014
  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:


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


Estimated Enrollment: 66
Study Start Date: May 2010
Estimated Primary Completion Date: November 2014 (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:Vitamen 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
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.
  • Age ≥ 18 years
  • 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
  • Age < 18 years
  • 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 (Cardiazem), 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

Contacts
Contact: Linda Cummings, MD 216-844-7334 linda.cummings@uhhospitals.org

Locations
United States, Ohio
University Hospitals Ahuja Medical Center Recruiting
Beachwood, Ohio, United States, 44122
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Linda Cummings, MD    216-844-7344    linda.cummings@uhhospitals.org   
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Prashanthi Thota, MD    216-444-7000    thotap@ccf.org   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Linda Cummings, MD Case Comprehensive Cancer Center
  More Information

No publications provided

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: May 28, 2014
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
Cholecalciferol
Ergocalciferols
Metformin
Omeprazole
Vitamin D
Vitamins
Anti-Ulcer Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Gastrointestinal Agents
Growth Substances
Hypoglycemic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014