Effect of Vitamin D Supplementation on 15-Prostaglandin Dehydrogenase Expression in Barrett's Esophagus
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Indefinite, LGD or no dysplasia arm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: Omeprazole (Drug)
Indefinite, LGD or no dysplasia arm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: Vitamin D3 (Drug)
Indefinite, LGD or no dysplasia arm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: upper endoscopy (Procedure)
high grade dysplasia
Barrett's esophagus with high grade dysplasia
干预措施: Omeprazole (Drug)
high grade dysplasia
Barrett's esophagus with high grade dysplasia
干预措施: Vitamin D3 (Drug)
high grade dysplasia
Barrett's esophagus with high grade dysplasia
干预措施: upper endoscopy (Procedure)
Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: Omeprazole (Drug)
Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: Vitamin D3 (Drug)
Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: upper endoscopy (Procedure)
Indefinite, LGD or no dysplasia arm:Vitamin D/Metformin Subarm
Barrett's esophagus patients who have no dysplasia or low grade dysplasia
干预措施: Metformin (Drug)
结局指标
主要结局
Arm 1(no or low grade dysplasia): 15-Prostaglandin dehydrogenase expression
时间窗: 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
时间窗: 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
次要结局
- effects on cyclooxygenase-2 expression(after 2 or 12 weeks after vitamin D supplement)
- 15-Prostaglandin dehydrogenase expression differences between RT-PCR and immunohistochemistry(after 2 or 12 weeks after vitamin D supplement)
- effects on levels of Ki-67(after 2 or 12 weeks after vitamin D supplement)
- effects on levels of caspase(after 2 or 12 weeks of vitamin D supplement)
- effects on insulin resistance(after 2 or 12 weeks of vitamin D supplement)
- decreased prostaglandin E2 expression in Barrett's esophagus(after 2 or 12 weeks of vitamin D supplement)