Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.
研究概览
简要总结
This is a randomized trial comparing the effect of oral simvastatin versus placebo on targets of the mevalonate pathway in men undergoing a prostatectomy as planned management for prostate cancer. Observed tissue effects will be correlated with changes in serum cholesterol and low-density lipoprotein.
详细描述
Prostate cancer patients that have chosen to undergo a prostatectomy as their primary treatment option will be recruited to this trial. Forty-four subjects will be randomized to either placebo or simvastatin (40 mg po/day) for 4 weeks prior to surgery. Serum samples will be obtained at baseline and immediately prior to prostatectomy. At prostatectomy, cancerous and benign prostate tissue will be microdissected and cryopreserved. Archival prostatectomy tissues will be used to construct tissue microarrays containing matched benign and malignant sections. The effect of HMG-CoA reductase inhibition on lipid raft cholesterol content and targets of prenylation will be determined. The incidence of apoptosis will be determined along with protein levels of mediators of apoptosis. Lastly the effect of statin therapy on cellular markers of proliferation will be determined.
Previously, we studied the effect of statin use on the risk of prostate cancer detection in a case-control study at the Portland VA Medical Center. Statin use was associated with a 62% reduction in cancer odds-risk (OR = 0.38, 95% CI 0.21-0.69). Although these epidemiologic and laboratory findings have generated enthusiasm for the study of statins in prostate cancer, no studies have examined the biologic effects of statins on prostate cancer in humans.
Hypothesis
Statin therapy prior to prostatectomy will successfully target the mevalonate pathway in the human prostate and this intervention will favorably alter tumor biomarker status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed prostatic adenocarcinoma with Gleason 5 to 7 (3+4 = 7 accepted, not 4 + 3 = 7)
- •Radical prostatectomy chosen as primary treatment for prostate cancer
- •Age 18 years or older
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Other preoperative or prior treatment directed at prostate cancer (i.e., Radiation, hormonal therapy, cryotherapy)
- •Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
- •History of or active liver disease or abnormal results of the baseline liver function test (> 2 x normal)
- •Current use of:
- •simvastatin
- •lovastatin
- •other HMG-CoA inhibitors
- •lipid-lowering agents
- •Amiodarone
- •Cholestyramine
- •Cholestyramine and colestipol (bile acid sequestrants)
- •Clofibrate and fenofibrate
- •Cyclosporine
- •CYP3A4 inhibitors
- •Diltiazem
- •Gemfibrozil
- •Niacin ( 1 g/day)
- •Verapamil and Warfarin
- •Known allergy or sensitivity to ingredients in simvastatin
研究组 & 干预措施
Simvastatin
Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
干预措施: Simvastatin (Drug)
Placebo
Twenty-two men will be on the placebo arm.
干预措施: Placebo (Other)
结局指标
主要结局
Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.
时间窗: 5 years
Measure the effect of pre-operative simvastatin versus placebo on the mevalonate pathway synthesis and target activation in benign and malignant prostate tissue using Androgen Receptor (AR) antibody. AR was measured in tissue obtained at the time of prostatectomy in both benign and malignant tissues.
次要结局
- Compare the Effect of Pre-operative Simvastatin Versus Placebo on Prostate Cancer Cell Apoptosis and Its Mediators in Men Undergoing Planned Prostatectomy.(2 years)