Urolithin A Supplementation for Prostate Cancer

Recruiting at 5 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Urolithin A, Pomegranate

Disqualifiers: Prior prostate cancer treatment, Alcohol dependency, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 3-6 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take urolithin A or pomegranate supplements during the study. Other supplements are allowed but must be documented.

How does the drug Urolithin A differ from other prostate cancer treatments?

Urolithin A is unique because it targets the androgen receptor, which is crucial in prostate cancer growth, and it is derived from natural dietary sources, potentially offering a less toxic alternative to traditional therapies. ^{1 2 3 4 5}

Research Team

Stephen Freedland, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

Men with confirmed prostate cancer scheduled for surgery can join this trial. They must have good blood counts, liver and kidney function, and controlled hepatitis or HIV if present. Men over 18 years old who haven't had prior treatments for prostate cancer or are taking similar supplements to Urolithin A are eligible.

Inclusion Criteria

Platelets >= 100,000/microliter

Absolute neutrophil count >= 1,000/microliter

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Higher levels allowed if due to known benign liver condition)

Exclusion Criteria

Participants with documented active alcohol and illegal substance dependency

History of allergic reactions to compounds similar to urolithin A

Participants receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Urolithin A or placebo orally twice daily for 3-6 weeks prior to radical prostatectomy

3-6 weeks

Regular visits for blood sample collection

Surgery

Participants undergo radical prostatectomy and biopsy at the time of surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Biopsy
• Biospecimen Collection
• Placebo Administration
• Urolithin A Supplement

Trial Overview The URO-PRO trial is testing whether a supplement called Urolithin A can reduce oxidative stress in the prostate before surgery compared to a placebo. Participants will take either the supplement or placebo daily for 3-6 weeks before their operation.

Participant Groups

Group I: Arm I (urolithin A) Experimental Treatment 3 Interventions

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 II: Arm II (placebo) Placebo Group 3 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Urolithin A (Uro-A) is a beneficial metabolite that helps reduce inflammation and may prevent cancer, derived from ellagic acid by gut bacteria.

The study reveals that during inflammation, Uro-A glucuronide (Uro-A glur) can be converted back to active Uro-A in tissues, enhancing its effectiveness in inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation. [2019]

IsoUro-A, a metabolite of ellagic acid, has been shown for the first time to inhibit the growth of human colon cancer cells (Caco-2) in a dose-dependent manner, although it is less effective than Urolithin A (Uro-A).

Both IsoUro-A and Uro-A induce cell cycle arrest and apoptosis in cancer cells, but IsoUro-A is more efficiently converted to inactive forms (glucuronidated) in these cells, which may reduce its antiproliferative effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism. González-Sarrías, A., Núñez-Sánchez, MÁ., García-Villalba, R., et al.[2018]

Urolithin B (UB) has shown potential in preventing colorectal cancer by remodeling the gut microbiome and enhancing the immune microenvironment, which includes increasing immune cell types like NK cells and decreasing PD-L1 levels.

When combined with standard chemotherapy drugs, UB improved treatment outcomes in colorectal cancer models, suggesting it could enhance the effectiveness of immunotherapy for CRC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B. Wang, L., Chen, J., Chen, Q., et al.[2023]

Urolithin A (UroA) effectively inhibits the growth of both androgen receptor-positive (AR+) and androgen receptor-negative (AR-) prostate cancer cells, with AR+ cells being more sensitive to its effects, indicating its potential as a targeted therapy for castration-resistant prostate cancer (CRPC).

Oral administration of UroA significantly reduced the growth of AR+ C4-2B xenografts in animal models without causing toxicity, and it works by downregulating androgen receptor signaling, suggesting its promise as a safe and effective treatment option for CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A natural molecule, urolithin A, downregulates androgen receptor activation and suppresses growth of prostate cancer. Dahiya, NR., Chandrasekaran, B., Kolluru, V., et al.[2020]

A new liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to accurately measure urolithin C levels in rat plasma, demonstrating high sensitivity and specificity with a calibration range of 4.95-1085 μg/L.

Urolithin C showed promising potential as an anti-diabetic treatment, with its main metabolites identified as glucuronyl and sulfate conjugates in plasma, indicating its metabolic processing in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the determination of urolithin C in rat plasma and its application to a pharmacokinetic study. Bayle, M., Roques, C., Marion, B., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A natural molecule, urolithin A, downregulates androgen receptor activation and suppresses growth of prostate cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Development and validation of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the determination of urolithin C in rat plasma and its application to a pharmacokinetic study. [2017]