This single-center, randomized, double-blind trial assesses the impact of short-term atorvastatin administration on proliferation activity, apoptotic rate and histological inflammation in prostate tissue.
In this trial 160 men who have been diagnosed with prostate cancer, and whose first-line treatment will be radical prostatectomy (surgical removal of the prostate), are randomized to receive either 80 mg atorvastatin or placebo daily for 2-5 weeks until the operation. Blood cholesterol and serum PSA are measured before starting the study drug use and before the operation. After the operation change in PSA and histological inflammation, apoptotic rate and Ki-67 staining intensity are compared between atorvastatin-treated and placebo-treated men. The correlation between changes in serum cholesterol or prostate specific antigen (PSA) and the tissue characteristics is evaluated. After recruiting 60 men we will perform an interim analysis on primary end-points without breaking the blinding to treatment allocation. If we observe a statistically significant difference in all primary end-points, the trial will be stopped early and the results published. Additionally, atorvastatin concentration in the blood and the prostate tissue is measured with mass spectrometry to determine penetrance of atorvastatin into the prostate. DNA- and RNA-samples are obtained from the prostate tissue and the blood. These will be used to study how gene expression of statin- and cholesterol-modifying enzymes affects the responses observed in prostate tissue. As a secondary end-point we will measure recovery of erectile function after the operation and compare between the two study arms. Erectile function is measured using IIEF-5 questionnaire once before the operation and again 3, 6, 9 and 12 months from the prostatectomy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
160
Capsules including 80 mg of atorvastatin
Similar capsules as in the atorvastatin arm, but without the active ingredient
Päijät-Häme Central Hospital
Lahti, Finland
Satakunta Central Hospital
Pori, Finland
Tampere University Hospital, Department of Urology
Tampere, Finland
Apoptosis
Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment
Time frame: Four weeks after recruitment
Ki-67 expression
Cellular proliferation activity in prostate tissue as measured by Ki-67 expression. Measured after radical prostatectomy, on average after 4 weeks of recruitment
Time frame: Four weeks after recruitment
Histological inflammation
Extent of histological inflammation in the prostate tissue as evaluated by study pathologist
Time frame: After prostatectomy
serum PSA
Change in serum PSA level as measured before starting the study drug and again just before prostatectomy
Time frame: At recruitment and before prostatectomy
serum cholesterol
Changes in measured fasting serum cholesterol parameters: total cholesterol, HDL and LDL. First measure is done at recruitment, another right before radical prostatectomy.
Time frame: At recruitment and again four weeks after
Atorvastatin level in prostate tissue
Measurement of atorvastatin level in prostate tissue with mass spectrometry. Measured after radical prostatectomy, on average four weeks after recruitment
Time frame: Four weeks after recruitment
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