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

NCT ID: NCT06022822

Last Updated: 2026-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-12

Study Completion Date

2027-05-01

Brief Summary

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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.

Detailed Description

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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.

IV. To collect stool samples for future analyses to determine the effect of Uro-A supplements on change in stool microbiome 16s ribosomal ribonucleic acid (rRNA) gene sequencing.

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.

Conditions

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Prostate Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Urolithin A Supplement

Intervention Type DIETARY_SUPPLEMENT

Given PO

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.

Group Type PLACEBO_COMPARATOR

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Placebo Administration

Intervention Type DRUG

Given PO

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Placebo Administration

Given PO

Intervention Type DRUG

Urolithin A Supplement

Given PO

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection Mitopure Uro-A Supplement

Eligibility Criteria

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Inclusion Criteria

* Participants must have pathologically confirmed adenocarcinoma of the prostate with formalin-fixed paraffin embedded (FFPE) biopsy tissue available for analysis. Diagnosis 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
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,000/microliter
* Platelets \>= 100,000/microliter
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) Note: Higher total bilirubin levels (=\< 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal
* Creatinine =\< 1.5 x institutional upper limit of normal
* 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen J Freedland

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

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Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Stephen J. Freedland

Role: primary

310-423-3974

Ashley E. Ross

Role: primary

312-694-1117

Scott E. Eggener

Role: primary

773-702-5195

Judd W. Moul

Role: primary

919-668-8108

David F. Jarrard

Role: primary

608-262-0759

Other Identifiers

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NCI-2023-03835

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI22-12-01

Identifier Type: OTHER

Identifier Source: secondary_id

NWU22-12-01

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189828

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA242643

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2023-03835

Identifier Type: -

Identifier Source: org_study_id

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