Statin Therapy Versus Placebo Prior to Prostatectomy
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Screening
|Official Title:||Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer|
- Measure the effect of pre-operative simvastatin versus placebo on the mevalonate pathway synthesis and target activation in benign and malignant prostate tissue. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Compare the effect of pre-operative simvastatin versus placebo on prostate cancer cell apoptosis and its mediators in men undergoing planned prostatectomy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
|Estimated Study Completion Date:||December 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1
Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
40 mg of simvastatin
Placebo Comparator: Arm 2
Twenty-two men will be on the placebo arm.
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.
|United States, North Carolina|
|Durham VA Medical Center, Durham, NC|
|Durham, North Carolina, United States, 27705|
|United States, Oregon|
|VA Medical Center, Portland|
|Portland, Oregon, United States, 97201|
|Principal Investigator:||Mark Garzotto, MD||VA Medical Center, Portland|