EGCG for Liver Cancer Prevention

(CATCH-B Trial)

Overseen By Yujin Hoshida, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: EGCG

Disqualifiers: Severe obesity, Active drinking, others

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether epigallocatechin gallate (EGCG), a compound in green tea, can help prevent liver cancer in individuals with liver cirrhosis. Participants take EGCG daily or a placebo (a pill with no active ingredients) for 24 weeks. The trial aims to determine if EGCG can prevent liver cancer and assess its safety for this use. Suitable candidates have been diagnosed with liver cirrhosis, have no history of liver cancer, and are not experiencing severe liver problems. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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

Research has shown that a compound in green tea, epigallocatechin gallate (EGCG), may help prevent cancer due to its safety and availability. Studies indicate that liver-related side effects from green tea extracts containing EGCG are uncommon.

For adults, safety studies consider a daily intake of 338 mg of EGCG safe. However, very high doses can cause liver damage. In this trial, participants will take between 600 mg and 800 mg per day, exceeding the usual safe amount.

While EGCG is generally safe for most people at normal doses, awareness of potential side effects at higher doses is crucial. Participants should follow the study guidelines carefully and report any unusual symptoms to the study team. ^{1 2 3 4 5}

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

Unlike the standard treatments for liver cancer prevention, which often involve surveillance or antiviral therapies, EGCG is derived from green tea and offers a natural alternative. Researchers are excited about EGCG because it targets cancer prevention by potentially reducing risk factors associated with liver cancer, such as inflammation and oxidative stress. Additionally, EGCG's oral administration makes it a convenient option for patients, offering a non-invasive and potentially safer approach compared to traditional methods.

What evidence suggests that EGCG might be an effective treatment for liver cancer prevention?

Research has shown that a compound in green tea called epigallocatechin gallate (EGCG) may help prevent liver cancer. Studies have found that EGCG can stop liver cancer cells from growing and can cause them to die. It also reduces liver inflammation and scarring in animal studies. This trial will evaluate EGCG's potential in preventing liver cancer in people with liver cirrhosis. Participants will receive either EGCG or a placebo for 24 weeks. Although more research is needed, these findings are promising for EGCG as a possible way to prevent liver cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Yujin Hoshida, MD, PhD

Principal Investigator

UT Southwestern

Are You a Good Fit for This Trial?

This trial is for adults over 18 with liver cirrhosis, a FIB-4 index above 3.25, and no history of liver cancer. They must have good blood, liver, and kidney function and be able to perform daily activities well. All genders and ethnicities are welcome if they don't have the HLA-B*35:01 gene or active worsening of their liver condition.

Inclusion Criteria

My gender or race does not exclude me from this trial.

I am able to care for myself but may not be able to do active work.

FIB-4 index > 3.25

Exclusion Criteria

History of adverse reaction to green tea products

Active drinking

I have used or am using EGCG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EGCG or placebo for 24 weeks, with potential dose adjustment at week 8 based on biomarker analysis

24 weeks

Monthly visits for adverse event monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including HCC incidence

1 year

Regular follow-up every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Epigallocatechin gallate (EGCG)

Trial Overview The study is testing EGCG's ability to prevent liver cancer in patients with cirrhosis. Participants will either receive EGCG or a placebo (a substance with no therapeutic effect) to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: Epigallocatechin gallate 600 - 800mg Experimental Treatment 1 Intervention

Epigallocatechin gallate (EGCG) 600mg will be administered daily via oral route for the initial 12 consecutive weeks on an outpatient basis. The dose of 600 mg will be continued for the second 12 weeks if an interim HCC biomarker test at the end of week 8 improves. If the interim test does not improve without dose-limiting adverse events, the dose will be increased to 800mg for the second 12 weeks, All participants will receive 24 weeks of treatment in total.

Group II: Placebo Placebo Group 1 Intervention

Oral administration of placebo for 24 weeks

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a study involving 72 C3H/HeNCrj mice, (-)-epigallocatechin gallate (EGCG) from green tea significantly reduced the incidence of liver tumors (hepatomas) from 83.3% in the control group to 56.0% and 52.2% in the groups receiving 0.05% and 0.1% EGCG, respectively.

EGCG was found to inhibit the growth and secretion of alpha-fetoprotein in human liver cancer cells without affecting their viability, suggesting that it could be a safe and effective preventive agent against liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effects of (-)-epigallocatechin gallate on spontaneous hepatoma in C3H/HeNCrj mice and human hepatoma-derived PLC/PRF/5 cells. Nishida, H., Omori, M., Fukutomi, Y., et al.[2019]

In a study involving C57BL/6 male mice, pretreatment with epigallocatechin-3-gallate (EGCG) significantly reduced liver injury caused by ischaemia-reperfusion, indicating its protective effects.

EGCG demonstrated antioxidant and antiapoptotic properties, as it improved biochemical markers of liver health and reduced oxidative stress and apoptosis-related changes after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death. Tak, E., Park, GC., Kim, SH., et al.[2018]

Epigallocatechin-3-gallate (EGCG) effectively reduces the viability of human hepatocellular carcinoma (HCC) cells, with significant decreases observed at concentrations of 50-400 microg/ml over 48 hours, indicating its potential as a therapeutic agent against liver cancer.

EGCG induces apoptosis in HCC cells by down-regulating the anti-apoptotic proteins COX-2 and Bcl-2, which activates caspase-9 and caspase-3, leading to increased cell death, demonstrating a clear mechanism of action for its anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epigallocatechin-3-gallate induces apoptosis in human hepatocellular carcinoma cells]. Chen, XL., Wang, Q., Cao, LQ., et al.[2013]

High doses of the tea polyphenol EGCG (1500 mg/kg) were found to cause significant liver toxicity in male CF-1 mice, leading to a 138-fold increase in plasma alanine aminotransferase (ALT) levels and an 85% reduction in survival rates.

Repeated daily doses of EGCG (750 mg/kg) further exacerbated liver damage, indicating that both the dose and frequency of EGCG administration are critical factors in its hepatotoxic effects, which are linked to oxidative stress and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Lambert, JD., Kennett, MJ., Sang, S., et al.[2021]

Epigallocatechin-3-gallate (EGCG), found in green tea, effectively induces apoptosis in human hepatocellular cancer cells (HCCLM6) while sparing non-cancerous liver cells, indicating its potential as a targeted cancer therapy.

The mechanism of action involves decreasing the expression of anti-apoptotic proteins (Bcl-2, NF-κB) and increasing pro-apoptotic factors (Bax, p53, caspases), leading to cell cycle arrest and mitochondrial dysfunction in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate induces the apoptosis of hepatocellular carcinoma LM6 cells but not non-cancerous liver cells. Zhang, Y., Duan, W., Owusu, L., et al.[2014]

Epigallocatechin gallate (EGCG), an antioxidant from green tea, was found to be toxic to liver cells (hepatocytes) at concentrations starting from 10 μmol/L in a study involving male Wistar rats.

While EGCG increased DNA synthesis in hepatocytes from rats that underwent partial hepatectomy (PHx), it also elevated the activity of caspases 3 and 7, indicating potential cell death, especially in the PHx group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of epigallocatechin gallate on hepatocytes isolated from normal and partially hepatectomized rats. Mezera, V., Kucera, O., Moravcova, A., et al.[2014]

Green tea infusions and green tea extract (GTE) products are generally considered safe for consumption, with no association between green tea intake and liver damage in humans, even at doses up to 450mg of EGCG per day.

A proposed tolerable upper intake level of 300mg of EGCG per person per day for food supplements provides a significant safety margin, as clinical studies have shown no liver effects at intakes below 600mg per day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements. Dekant, W., Fujii, K., Shibata, E., et al.[2017]

In a study using male Wistar rats with chemically induced liver damage, EGCG (a compound from green tea) was found to be well-tolerated and significantly reduced liver inflammation and tumor formation associated with hepatocellular carcinoma (HCC).

EGCG not only improved liver function markers but also inhibited the progression of fibrosis by affecting specific liver cell types, suggesting its potential as a chemopreventive agent against HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma. Sojoodi, M., Wei, L., Erstad, DJ., et al.[2021]

In a study involving Balb/C mice, EGCG (10 or 30 mg/kg) was shown to significantly reduce liver injury caused by concanavalin A (ConA)-induced hepatitis by lowering inflammatory markers and protecting against cell death.

EGCG's protective effects are linked to its ability to inhibit the IL-6/JAKs/STAT3 pathway, which in turn reduces apoptosis and autophagy mediated by BNIP3, highlighting its potential as a therapeutic agent for liver inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3. Li, S., Xia, Y., Chen, K., et al.[2022]

(-)-Epigallocatechin-3-gallate (EGCG), a compound found in green tea, effectively inhibits the growth of colorectal cancer cells and induces cell death, showing promise as a chemotherapy agent against liver metastases.

In a study involving human colorectal cancer cell lines and SCID mice, EGCG not only reduced liver metastasis without causing weight loss or liver damage but also suppressed blood vessel formation in tumors, indicating its potential safety and efficacy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer. Maruyama, T., Murata, S., Nakayama, K., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6387605/

Epigallocatechin-3-gallate in the prevention and treatment ... Accumulating preclinical evidence has shown that EGCG inhibits the growth and induces apoptosis of different liver cancer cells by acting via ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10244546/

The potential of epigallocatechin gallate in ... - PubMed Central Accumulating evidence has confirmed EGCG prevents and inhibits the hepatic tumorigenesis and progression through multiple biological mechanisms.

3. aacrjournals.org aacrjournals.org/cancerpreventionresearch/article/13/6/497/47451/Epigallocatechin-Gallate-Induces-Hepatic-Stellate

Epigallocatechin Gallate Induces Hepatic Stellate Cell ... Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its ...

4. pubs.acs.org pubs.acs.org/doi/10.1021/acsomega.5c00839

A Comparative Analysis of Monolayer vs Multicellular Tumor ... These data suggest that HepG2 cells resemble a broader group of cell lines that exhibit a coordinated response to EGCG treatment, characterized ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1756464620303960

A review on anti-cancer effect of green tea catechins (-)-Epigallocatechin gallate suppresses the growth of human hepatocellular carcinoma cells by inhibiting activation of the vascular endothelial growth ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4082721/

Green tea catechin, epigallocatechin-3-gallate (EGCG) EGCG has great potential in cancer prevention because of it's safety, low cost and bioavailability. In this review, we discuss its cancer preventive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5193539/

Liver-related safety assessment of green tea extracts in ... Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0273230018300928

The safety of green tea and green tea extract consumption ... A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose.

9. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/EGCG-Cognitive-Vitality-For-Researchers.pdf

Epigallocatechin Gallate (EGCG) Safety: EGCG supplements are considered safe for most people when taking physiologic doses, but high doses have been associated with elevated liver enzymes.

10. healthline.com healthline.com/nutrition/egcg-epigallocatechin-gallate

EGCG (Epigallocatechin Gallate): Benefits, Dosage, and ... However, some reports suggest that very high doses of EGCG may lead to liver toxicity in animals and humans. Higher doses may be more easily ...