A Prospective Placebo-control Double-blind Randomized Trial of Metformin in Chemoprevention of Metachronous Colonic Neoplastic Polyps
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Percentage of Ki-67-Stained Nuclei in Normal Rectal Mucosa
研究概览
简要总结
The goal of this clinical research study is to learn if metformin extended release (ER) can prevent colonic adenomas from becoming cancerous. Metformin ER will be compared to a placebo.
Metformin ER is designed to block a protein in tumor cells that is important in tumor growth and blood vessel development. This may cause cell death or reduce the spread of the disease.
A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
详细描述
Colonic adenomas are considered pre-cancerous, but they may change into colorectal cancer. Patients have a higher risk of developing additional adenomas if adenomas are found at the time of their follow-up colonoscopy.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being assigned to either group.
If you are in Group 1, you will receive metformin ER
If you are in Group 2, you will receive a placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 40 and 75 years
- •Polyp features suggesting high risk for recurrence include: piece-meal polypectomy, large (>10mm) neoplastic polyp, polyp with high grade dysplasia, or substantial number (>10) of neoplastic polyps.
- •ability to give informed consent
- •Patients should be registered on LAB10-0417
- •Diabetic patients are eligible but they may be excluded if they are taken Metformin, insulin or sulfonylureas
排除标准
- •Patients with renal insufficiency defined as serum creatinine >= 1.4 mg/dl for females and >= 1.5 mg/dl for males by the manufacturer.
- •Pregnant or nursing women
- •A malignancy currently under active therapy
- •Unstable angina, uncontrolled ischemic cardiac disease or symptomatic congestive heart failure (e.g. Class III or IV New York Heart Association's Functional Classification)
- •Current usage of Metformin
- •Current usage of insulin, sulfonylureas
- •History of lactic acidosis
- •Liver dysfunction including chronic active hepatitis and cirrhosis
- •Inability to give informed consent
- •Other investigational drugs within the past one year or concurrently
- •Known hypersensitivity or intolerance to Metformin
- •Contraindications for repeat colonoscopy
- •Inflammatory bowel disease
- •Rectosigmoiditis of any etiology
研究组 & 干预措施
Metformin ER
Participants receive two tablets of Metformin ER 500 mg once daily for no more than twelve to eighteen months allowing time for at least one follow up colonoscopy. Dose will be reached in a gradual escalation scheme to improve gastrointestinal tolerance. If participants experience side effects during dose escalation regimen, they will be reduced to one tablet of 500 mg daily, and may continue taking 500 mg daily for the duration of the study.
干预措施: Metformin ER (Drug)
Placebo
Control group given matched Placebo once daily for no more than twelve to eighteen months allowing time for at least one follow up colonoscopy.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Ki-67-Stained Nuclei in Normal Rectal Mucosa
时间窗: 3 months
Primary endpoint defined as change in overall proliferation index between baseline and first return visit, that is, percentage of Ki-67-stained nuclei, in normal rectal mucosa. Tissue samples will be obtained at baseline colonoscopy and subsequent exams for analysis including Ki67, caspase 3, and various biomarkers and immunohistochemicals studies.
次要结局
未报告次要终点