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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

Tracking Information
First Submitted Date  ICMJE November 1, 2011
First Posted Date  ICMJE November 4, 2011
Last Update Posted Date March 10, 2016
Study Start Date  ICMJE May 2010
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2011)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
  • 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
  • affects 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
  • 15-Prostaglandin dehydrogenase expression differs 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
  • affects 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
  • affects 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
  • affects 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
Official Title  ICMJE Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Short Segment Barrett's Esophagus
  • Long Segment Barrett's Esophagus
Intervention  ICMJE
  • 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
  • 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.
  • 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
Study Arms  ICMJE
  • Experimental: Indefinite, LGD or no dysplasia arm
    Barrett's esophagus patients who have no dysplasia or low grade dysplasia
    Interventions:
    • Drug: Omeprazole
    • Drug: Vitamin D3
    • Procedure: upper endoscopy
  • Experimental: high grade dysplasia
    Barrett's esophagus with high grade dysplasia
    Interventions:
    • Drug: Omeprazole
    • Drug: Vitamin D3
    • Procedure: upper endoscopy
  • Experimental: Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
    Barrett's esophagus patients who have no dysplasia or low grade dysplasia
    Interventions:
    • Drug: Omeprazole
    • Drug: Vitamin D3
    • Procedure: upper endoscopy
    • Drug: Metformin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2016)
26
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2011)
20
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01465113
Other Study ID Numbers  ICMJE CASE12209
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Linda Cummings, MD Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP