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Statin Therapy Versus Placebo Prior to Prostatectomy

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ClinicalTrials.gov Identifier: NCT00572468
Recruitment Status : Completed
First Posted : December 13, 2007
Results First Posted : July 13, 2017
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE December 11, 2007
First Posted Date  ICMJE December 13, 2007
Results First Submitted Date  ICMJE April 17, 2017
Results First Posted Date  ICMJE July 13, 2017
Last Update Posted Date July 13, 2017
Study Start Date  ICMJE December 2007
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2017)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2007)
Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.
Change History Complete list of historical versions of study NCT00572468 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2017)
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 ]
Compare the effect of pre-operative simvastatin versus placebo on prostate cancer cell apoptosis and its mediators in men undergoing planned prostatectomy. Apoptosis was measured by calculating the percent of Ki67 cellular staining.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2007)
Compare the Effect of Pre-operative Simvastatin Versus Placebo on Prostate Cancer Cell Apoptosis and Its Mediators in Men Undergoing Planned Prostatectomy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Statin Therapy Versus Placebo Prior to Prostatectomy
Official Title  ICMJE Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Screening
Condition  ICMJE
  • Cancer
  • Prostate Cancer
Intervention  ICMJE
  • Drug: Simvastatin
    40 mg of simvastatin
    Other Name: statin
  • Other: Placebo
    placebo
Study Arms  ICMJE
  • Active Comparator: Simvastatin
    Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
    Intervention: Drug: Simvastatin
  • Placebo Comparator: Placebo
    Twenty-two men will be on the placebo arm.
    Intervention: Other: Placebo
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: June 13, 2017)
42
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2007)
44
Actual Study Completion Date  ICMJE April 30, 2017
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
    • Danazol
    • Diltiazem
    • Gemfibrozil
    • Niacin ( 1 g/day)
    • Verapamil and Warfarin
  • Known allergy or sensitivity to ingredients in simvastatin
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 21 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 NCT00572468
Other Study ID Numbers  ICMJE CLIN-013-07S
VA IRB#1735 ( Other Identifier: VA IRB )
SOL-07130-L ( Other Identifier: OHSU Knight Cancer Institute Identifier )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE Oregon Health and Science University
Investigators  ICMJE
Principal Investigator: Mark Garzotto, MD VA Medical Center, Portland
PRS Account VA Office of Research and Development
Verification Date June 2017

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