Glycyrrhizin for Prostate Cancer

(GU-01 Trial)

Overseen By Omer Qazi, MBBS

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must not be taking: CYP3A4 inhibitors, QT prolonging drugs

Disqualifiers: Concurrent malignancy, Previous chemotherapy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks (+/- 2 weeks)

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Glycyrrhizin for men recently diagnosed with prostate cancer who plan to undergo prostate removal surgery. Researchers aim to determine if Glycyrrhizin, administered in two different doses, can help manage prostate cancer before surgery. Participants will receive either a placebo or one of two doses of Glycyrrhizin for six weeks. This trial suits those who have not yet received any treatment for their prostate cancer and are preparing for surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a 1-week period without taking certain medications that affect the liver enzyme CYP3A4. Also, you cannot take medications that affect heart rhythm (QT interval).

Is there any evidence suggesting that Glycyrrhizin is likely to be safe for humans?

Research has shown that glycyrrhizin, a substance in licorice root, affects cancer cells. Past studies found that it targets prostate cancer cells and might help reduce inflammation, often linked to cancer growth.

Importantly, glycyrrhizin reduced certain side effects commonly seen in cancer treatment, such as risks to the kidneys, liver, and nerves, suggesting it is generally well-tolerated.

While the current trial focuses on its use for prostate cancer, the safety of glycyrrhizin in other contexts provides some reassurance. However, monitoring for any negative effects during the trial remains crucial. ^{1 2 3 4 5}

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

Unlike the standard treatments for prostate cancer, which often involve hormone therapy, surgery, or radiation, Glycyrrhizin offers a novel approach due to its origin as a natural compound derived from licorice root. Researchers are particularly excited about Glycyrrhizin because it may have anti-inflammatory and anti-cancer properties, potentially offering a less invasive option with fewer side effects. Additionally, Glycyrrhizin's unique mechanism of action involves modulating immune responses, which could complement existing therapies and enhance their effectiveness. This could pave the way for more personalized treatment strategies for prostate cancer patients.

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

Research has shown that glycyrrhizin, a substance in licorice, may help fight prostate cancer. Studies indicate it can slow the growth of prostate cancer cells by inducing natural cell death. It also reduces certain genes linked to inflammation in these cancer cells, which is beneficial because inflammation can worsen cancer. Glycyrrhizin's ability to reduce inflammation and fight cancer makes it a promising option for treating various cancers, including prostate cancer. In this trial, participants will be randomized into different arms, with some receiving glycyrrhizin at varying doses to evaluate its effectiveness in managing prostate cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Natalie Reizine

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for men over 18 with untreated prostate cancer who are fit enough for daily activities and can undergo surgery. They must be able to give consent, release health information, and agree to use barrier contraception during the study.

Inclusion Criteria

Willing to use barrier contraceptive method during study intervention

Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization

I have been diagnosed with prostate cancer.

Exclusion Criteria

I don't have any other cancers that could affect this treatment's safety or results.

I haven't had cancer treatments or experimental drugs in the last 30 days.

I have not taken strong or moderate CYP3A4 inhibitors or inducers in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Glycyrrhizin (GLY) at varying doses or are observed for 6 weeks prior to surgery

6 weeks (+/- 2 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in various biomarkers and patient perspectives

2 months

What Are the Treatments Tested in This Trial?

Interventions

• Glycyrrhizin

Trial Overview

The study tests Glycyrrhizin (a compound from licorice root) against no treatment in men awaiting prostate surgery. Participants are randomly assigned to either receive Glycyrrhizin or just observation without any active treatment before their operation.

How Is the Trial Designed?

Group I: Glycyrrhizin Arm 3 (Dose Level 2) Experimental Treatment 1 Intervention

25 participants will be randomized to receive 150mg daily for 6 weeks (+/- 2 weeks)

Group II: Glycyrrhizin Arm 2 (Dose Level 1) Experimental Treatment 1 Intervention

25 participants will be randomized to receive 75mg daily for 6 weeks (+/- 2 weeks)

Group III: Observational Arm 1 (Dose Level 0) Placebo Group 1 Intervention

10 participants will be randomized to observational arm

Glycyrrhizin is already approved in Japan, China, United States, Canada for the following indications:

Approved in Japan as Glycyrrhizic acid for:

• Chronic hepatitis

Approved in China as Glycyrrhizic acid for:

• Chronic hepatitis

Approved in United States as Glycyrrhizic acid for:

• Food sweetener

Approved in Canada as Glycyrrhizic acid for:

• Over-the-counter products (status canceled post-marketed)

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

18α-glycyrrhetinic acid (AGA) effectively inhibits the growth of androgen-independent metastatic prostate cancer cells (DU-145) by inducing apoptosis, as shown through flow cytometry analyses.

AGA also reduces cancer cell invasion and angiogenesis by down-regulating key proteins involved in inflammation and cancer progression, suggesting its potential as a promising agent for prostate cancer treatment and prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes. Shetty, AV., Thirugnanam, S., Dakshinamoorthy, G., et al.[2022]

In a study of 1476 prostate cancer patients over an average of 10.8 years, serum levels of vitamin D (25(OH)D) were not linked to the risk of disease recurrence or prostate cancer-specific mortality.

However, low vitamin D levels were associated with a higher risk of death from causes other than prostate cancer, suggesting that while vitamin D may not impact prostate cancer outcomes, it could influence overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis. Holt, SK., Kolb, S., Fu, R., et al.[2021]

Glycyrrhizic acid (GA) effectively inhibits the proliferation of gastric cancer (GC) cells in a time- and dose-dependent manner, leading to cell cycle arrest and apoptosis.

GA induces apoptosis by altering key proteins involved in cell cycle regulation and apoptosis, including down-regulating cyclins and Bcl-2, while affecting the PI3K/AKT signaling pathway, suggesting its potential as an anti-cancer treatment for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis. Wang, H., Ge, X., Qu, H., et al.[2022]

Glycyrrhetinic acid (GA) significantly reduces the proliferation of LNCaP androgen-dependent prostate cancer cells, suggesting its potential as a targeted treatment for this type of cancer.

GA also decreases the production of prostate-specific antigen (PSA) in LNCaP cells, indicating its possible role in managing prostate cancer markers, while showing no effect on androgen-independent cancer cells like PC3 and DU145.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. Hawthorne, S., Gallagher, S.[2013]

Glycyrrhizic acid, commonly used as a sweetener, is converted in the body to glycyrrhetic acid, which is significantly more potent and can lead to toxicity, including hypertension and electrolyte disturbances.

The absorption and reabsorption of glycyrrhetic acid are influenced by gastrointestinal transit times, suggesting that individuals with slower transit may be at higher risk for adverse effects from glycyrrhizic acid, making this a potential factor to monitor in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Ploeger, B., Mensinga, T., Sips, A., et al.[2022]

Glycyrrhizin, a compound from licorice roots, shows significant potential in reducing the viability of human prostate cancer cells (LNCaP and DU-145) in vitro, demonstrating a time- and dose-dependent inhibition of cell proliferation.

The mechanism of action appears to involve apoptosis, as indicated by DNA damage and flow cytometric analyses, but does not rely on caspase-3 and -8 pathways, suggesting alternative apoptotic mechanisms may be at play.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Thirugnanam, S., Xu, L., Ramaswamy, K., et al.[2013]

Isoliquiritigenin, a flavonoid from Glycyrrhiza glabra L., effectively inhibits the growth of prostate cancer cell lines DU145 and LNCaP in a dose- and time-dependent manner.

The compound induces cell cycle arrest at the S and G2/M phases and enhances the expression of GADD153, suggesting that GADD153 is a key player in the anti-tumor effects of isoliquiritigenin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isoliquiritigenin inhibits the growth of prostate cancer. Kanazawa, M., Satomi, Y., Mizutani, Y., et al.[2019]

In a study of chronic prostatitis treatment, 84% of patients improved when treated with the traditional Chinese medicine Hachimi-ji-ji-oh-gan alongside sulfamethoxazole-trimethoprim, compared to 53% improvement with sulfamethoxazole-trimethoprim alone.

Hachimi-ji-ji-oh-gan appears to enhance the effectiveness of antimicrobial agents by potentially altering prostatic tissue or fluid characteristics, although it does not have direct antimicrobial properties itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined treatment of chronic prostatitis with sulfamethoxazole-trimethoprim and hachimi-ji-oh-gan]. Kaneko, S., Akiyama, T., Kurita, T.[2013]

In a phase II clinical trial involving 70 participants (36 receiving isoflavones and 34 receiving placebo), isoflavones were well tolerated but did not significantly reduce tissue markers of prostate cancer proliferation, indicating limited efficacy in this regard.

Isoflavone supplementation led to a significant reduction in serum PSA levels in Caucasian men, but this effect was not observed in African American men, highlighting potential differences in response to treatment based on ethnicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy. Kumar, NB., Pow-Sang, J., Spiess, P., et al.[2020]

In a mouse model of prostate cancer, combining dietary soy with calcitriol (active vitamin D) significantly inhibited tumor growth more than either treatment alone, suggesting a synergistic effect.

However, this combination also raised concerns about safety, as it led to dangerously high levels of calcium in the blood (hypercalcemia) and potential toxicity, highlighting the need for caution when using these supplements together in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of calcitriol and dietary soy exhibits enhanced anticancer activity and increased hypercalcemic toxicity in a mouse xenograft model of prostate cancer. Wang, JY., Swami, S., Krishnan, AV., et al.[2021]

Glycyrrhizic acid (GA) demonstrated significant chemopreventive effects against colon tumor development in Wistar rats, as it reduced tumor incidence and multiplicity when administered at a dose of 15 mg/kg over a 30-week period.

GA treatment improved key biological markers associated with cancer progression, such as decreasing pro-inflammatory cytokines and enhancing apoptotic responses, suggesting its potential as a safe and effective intervention against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycyrrhizic acid suppresses 1,2-dimethylhydrazine-induced colon tumorigenesis in Wistar rats: Alleviation of inflammatory, proliferation, angiogenic, and apoptotic markers. Khan, R., Rehman, MU., Khan, AQ., et al.[2019]

Prostate cancer is primarily driven by androgens and androgen receptors, and while advancements in treatment have improved patient outcomes, over 20% of patients still develop aggressive, treatment-resistant forms of the disease.

Natural products from edible plants and other sources, known as nutraceuticals, show promise as therapies for prostate cancer due to their ability to target multiple mechanisms involved in cancer progression, potentially offering lower toxicity and greater efficacy compared to traditional synthetic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Kallifatidis, G., Hoy, JJ., Lokeshwar, BL.[2018]

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pmc.ncbi.nlm.nih.gov

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8857760/

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sciencedirect.com

sciencedirect.com/science/article/pii/S0006291X25007764

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tandfonline.com

tandfonline.com/doi/full/10.1080/17460441.2021.1956901

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frontiersin.org

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Advances in the roles of glycyrrhizic acid in cancer therapy

GL could inhibit a series of side effects such as nephrotoxicity, hepatotoxicity, genotoxicity, neurotoxicity and lung toxicity in cancer treatment by ...

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Our results Suggested that 18β-GA in Glycyrrhiza radix could inhibit the proliferation and metastasis of GC by promoting cell apoptosis, ...