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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Urolithin A, a supplement, can reduce oxidative stress in prostate cancer tissues before surgery. Participants will take either Urolithin A or a placebo for 3 to 6 weeks. It targets men with biopsy-confirmed prostate cancer who are scheduled for surgery and have not received prior treatment for their cancer. The goal is to determine if the supplement has an effect compared to the placebo. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Urolithin A supplementation is likely to be safe for humans?

Research has shown that Urolithin A, the main treatment in this trial, has been studied for safety in humans. Previous studies found that Urolithin A is generally well-tolerated, meaning most people can take it without problems. In these studies, no major safety concerns or serious side effects were reported.

Urolithin A is a substance the body naturally produces when consuming foods like pomegranates, which are rich in ellagic acid. This indicates that the body is somewhat familiar with it. Some research has examined its effects on prostate cancer cells and found it promising, without showing any major safety issues.

Although this trial is in the early stages, testing Urolithin A in humans suggests that earlier safety findings are positive. If Urolithin A had not been safe in initial studies, it would not have progressed to more advanced testing in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard of care for prostate cancer, which often involves surgery, radiation, or hormone therapy, Urolithin A is derived from natural compounds found in fruits like pomegranates. Researchers are excited about Urolithin A because it targets cellular health by enhancing mitochondrial function, potentially offering a new way to combat cancer cell growth. This approach is different because it focuses on improving overall cell energy and health, rather than directly attacking cancer cells. If successful, it could offer a complementary strategy to existing treatments with fewer side effects.

What evidence suggests that Urolithin A might be an effective treatment for prostate cancer?

Research suggests that Urolithin A (Uro-A), which participants in this trial may receive, might help treat prostate cancer. Studies have found that Uro-A can induce the death of prostate cancer cells by affecting a process involving p53, a protein that regulates cell growth. Other research shows that drinking pomegranate juice, which contains substances that convert into Urolithin A in the body, can slow the increase of prostate-specific antigen (PSA) levels, potentially slowing cancer progression. Additionally, drinking pomegranate juice has been linked to better outcomes in prostate cancer. These findings suggest that Uro-A could reduce oxidative stress, a harmful process that can damage cells. ^{3 6 7 8 9}

Who Is on the Research Team?

Stephen Freedland, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19885850/

Occurrence of urolithins, gut microbiota ellagic acid ... Our aim was to assess whether ETs or their metabolites ellagic acid and urolithins reach the human prostate upon consumption of ET-rich foods.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31177307/

Urolithin A induces prostate cancer cell death in p53- ... The purpose of this study was to investigate the influence of UA on the p53-MDM2 interaction pathway in prostate cancer cell lines.

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/1934578X241310020

Implications for Urolithin Combination Therapy The synthesis of mUroA (3-hydroxy-8-methoxy-6H-dibenzo-[b,d]pyran-6-one) was achieved through a reaction involving 2-bromo-5-methoxybenzoic acid ...

4. pubs.acs.org pubs.acs.org/doi/10.1021/jf071303g

Pomegranate Ellagitannin-Derived Metabolites Inhibit ... Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer ...

5. researchgate.net researchgate.net/publication/38063883_Occurrence_of_urolithins_gut_microbiota_ellagic_acid_metabolites_and_proliferation_markers_expression_response_in_the_human_prostate_gland_upon_consumption_of_walnuts_and_pomegranate_juice

Occurrence of urolithins, gut microbiota ellagic acid ... Previous studies demonstrated that consumption of pomegranate juice and extracts can ameliorate clinical outcomes in prostate cancer, examining ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17722872/

Pomegranate Ellagitannin-Derived Metabolites Inhibit ... Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) ...

7. thegoodscentscompany.com thegoodscentscompany.com/data/rw1661721.html

urolithin A 6H-dibenzo[b,d]pyran-6-one, 3,8-dihydroxy PubMed:Urolithin A causes p21 up-regulation in prostate cancer cells. PubMed:In vitro antiproliferative and antioxidant effects of urolithin A, the colonic ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.200900152

Occurrence of urolithins, gut microbiota ellagic acid ... Our aim was to assess whether ETs or their metabolites ellagic acid and urolithins reach the human prostate upon consumption of ET-rich foods ...

9. tga.gov.au tga.gov.au/resources/resources/compositional-guidelines/urolithin

Urolithin A Description. Urolithin A is a synthetic version of urolithin A of the compound formed endogenously following consumption of ellagic acid and ...