Placebo-Controlled Trial of Urolithin A Supplementation in Men With Prostate Cancer Undergoing Radical Prostatectomy, URO-PRO Trial
Purpose
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.
Condition
- Prostate Adenocarcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Male
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
Recruiting Locations
Los Angeles, California 90048
Chicago, Illinois 60611
Chicago, Illinois 60637
Durham, North Carolina 27710
Madison, Wisconsin 53792
More Details
- NCT ID
- NCT06022822
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
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.