Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial

A Phase 2 Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Placebo Administration; Dietary supplement: Urolithin A Supplement; Procedure: Biopsy Procedure

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effect of a 3-to-6-week intervention of urolithin A (Uro-A) supplements versus placebo on 8-OHdG percent positive change in prostate cancer tumor tissue obtained by core needle biopsy in participants who undergo radical prostatectomy after 3 to 6 weeks of therapy.

SECONDARY OBJECTIVES:

I. To determine prostate tissue and plasma concentrations of Uro-A, urolithin sulfate and urolithin A glucuronide, as 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-study tissue only).

II. To compare the change in expression of cell cycle genes in prostate cancer tumor tissue from pre-study biopsy to radical prostatectomy in men receiving Uro-A supplements for 3 to 6 weeks and a control group of men receiving a placebo.

III. To determine the effect of Uro-A supplements on change in 8-OHdG expression in benign and tumor-adjacent prostatic tissue from pre-study biopsy to radical prostatectomy (RP) following 3-6 weeks of therapy in comparison to a control group of men receiving a placebo.

EXPLORATORY OBJECTIVES:

I. To determine the effect of Uro-A supplements on circulating levels of high sensitivity C-reactive protein (hsCRP), TNF-alpha, and IL-6, as measured by change from baseline to end-of-study compared with the men receiving a placebo.

II. To compare change in tumor gene expression patterns of Hallmark androgen signaling between study arms.

III. To determine the effect of a 3-to-6-week intervention of urolithin A (Uro-A) supplements versus placebo on 8-OHdG H-index (percent staining positive at each score in a 0-3 scale) change in prostate cancer tumor tissue obtained by core needle biopsy at baseline and at radical prostatectomy after 3 to 6 weeks of therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive urolithin A orally (PO) twice daily (BID) for 3-6 weeks prior to standard of care (SOC) RP. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study.

ARM II: Patients receive placebo orally (PO) twice daily (BID) for 3-6 weeks prior to SOC RP. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study.

Patients are followed up at 2 weeks after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Stephen J. Freedland; Phone Number: 310-423-3974; Email: Stephen.Freedland@cshs.org
      • Principal Investigator: Stephen J. Freedland
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Comprehensive Cancer Center
      • Principal Investigator: Abhinav Sidana
      • Contact: Abhinav Sidana; Phone Number: 773-702-1860; Email: abhinav.sidana@bsd.uchicago.edu
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Ashley E. Ross
      • Contact: Ashley E. Ross; Phone Number: 312-694-1117; Email: ashley.ross1@northwestern.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Judd W. Moul; Phone Number: 919-668-8108; Email: judd.moul@duke.edu
      • Principal Investigator: Judd W. Moul
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center - University Hospital
      • Contact: David F. Jarrard; Phone Number: 608-262-0759; Email: jarrard@urology.wisc.edu
      • Principal Investigator: David F. Jarrard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
• Scheduled to undergo RP in the next 3-6 weeks
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• 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
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to urolithin A
• Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (urolithin A); Patients receive urolithin A PO BID for 3-6 weeks prior to SOC RP. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Dietary supplement: Urolithin A Supplement; Given PO; Other Names: Mitopure; Uro-A Supplement; Procedure: Biopsy Procedure; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy
Placebo Comparator: Arm II (placebo); Patients receive placebo PO BID for 3-6 weeks prior to SOC RP. Patients also undergo biopsy at time of surgery and collection of blood samples during screening and on study.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Placebo Administration; Given PO; Procedure: Biopsy Procedure; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to radical prostatectomy (RP) after 3 to 6 weeks of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to RP after 3 to 6 weeks of therapy
Changes in 8-OHdG expression		Baseline up to RP after 3 to 6 weeks of therapy
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.	Baseline up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephen J Freedland, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy; Specimen Handling
• Other Study ID Numbers: NCI-2023-03835 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA060553 (U.S. NIH Grant/Contract); UG1CA242643 (U.S. NIH Grant/Contract); UG1CA189828 (U.S. NIH Grant/Contract); NCI22-12-01 (Other Identifier: Northwestern University); NWU22-12-01 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No