This phase II randomized control trial assesses the effect of Urolithin A (Uro-A) supplementation compared to placebo in men with biopsy-confirmed prostate cancer undergoing radical prostatectomy (RP) progressive disease. A total of 90 men will be accrued and randomized 1:1 to receive a 1000 mg daily dose of Uro-A in two 250 mg capsules PO BID or two placebo capsules BID daily for 3 to 6 weeks prior to RP. The primary endpoint is to determine the effect of Uro-A on decreasing prostate tumor tissue oxidative stress (measured by 8-OHdG) compared to placebo.
Participants who have pathologically confirmed adenocarcinoma of the prostate with formalin-fixed paraffin embedded (FFPE) biopsy tissue available for analysis, including those on active surveillance. Most recent biopsy can be any time in the six months prior to registration/randomization
Participants >= 18 years will be enrolled. Because no dosing or adverse event (AE) data are currently available on the use of urolithin A in participants < 18 years of age, children and adolescents are excluded from this study
Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Participants with prior primary treatment or hormonal therapy for prostate cancer (PC)
Participants with documented active alcohol and illegal substance dependency
Participants already receiving urolithin A (Mitopure, commercially available in the United States), or pomegranate supplements. Note: Other supplements are allowed but must be documented
Participants receiving any other investigational agents
Parallel
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Placebo Administration
DrugGiven PO
Urolithin A Supplement
Dietary supplementGiven PO
Percent positive change in 8-OHdG
The primary endpoint will be analyzed using a linear regression model. Standard descriptive statistics, including mean, standard deviation, median and interquartile range for continuous variables, and frequency and percent for categorical variables, will be used to summarize baseline variables by treatment arm. Changes will be summarized similarly. Graphical techniques, including boxplots and histograms, will be used to examine the distribution and to assess assumptions made for the primary analysis.
Changes in prostate tissue and plasma concentrations of urolithin A (Uro-A), urolithin sulfate and urolithin A glucuronide
Measured by change from baseline to end-of-study, in comparison to changes from baseline to end-of-study in a control group receiving a placebo (except tissue levels, which will be compared between arms using end-of-tissue only). Will be analyzed using the same approach as the analysis of the primary endpoint. Changes in plasma concentrations of Uro-A, urolithin sulfate and urolithin A glucuronide, from baseline to radical prostatectomy will be estimated and summarized using standard descriptive statistics.
Changes in expression of cell cycle genes
The ribonucleic sequencing will be used to compute a single z-score (i.e. one data point per patient) which will represent the composite expression of 31 cell-cycle genes.
Changes in 8-OHdG expression
Click on the lead sponsor to view all of their trials.
