Text Size

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

This study is currently recruiting participants.
Verified April 2013 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: April 29, 2013
Last verified: April 2013
History of Changes
  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
 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:

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


Estimated Enrollment: 20
Study Start Date: May 2010
Estimated Primary Completion Date: August 2013 (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.

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 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

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
  Contacts and Locations
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: April 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:
Barrett's Esophagus
Vitamin D3
cholecalciferol
15-Prostaglandin Dehydrogenase Expression

Additional relevant MeSH terms:
Barrett Esophagus
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Omeprazole
Proton Pump Inhibitors
 Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013