EGCG for Pulmonary Fibrosis

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Sydney Montesi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Hal Chapman

Must be taking: Nintedanib, Pirfenidone

Must not be taking: Corticosteroids, Digoxin

Disqualifiers: HCV, HBV, Emphysema, Alcohol, others

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing EGCG, a compound from green tea, in patients with idiopathic pulmonary fibrosis (IPF). The goal is to see if EGCG can safely reduce lung scarring. EGCG works by blocking harmful signals that cause lung tissue to harden. Epigallocatechin-3-gallate (EGCG) is a polyphenol and a major component of green tea, known for its potent antioxidant, anti-inflammatory, and anti-fibrotic properties.

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

You must have been on a stable dose of nintedanib or pirfenidone for at least 12 weeks before starting the trial, and you cannot take digoxin during the study. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

What evidence supports the effectiveness of the drug EGCG for treating pulmonary fibrosis?

Research shows that EGCG can reduce harmful signaling pathways and inflammation in lung tissues, which are involved in pulmonary fibrosis. It also helps break down excess collagen, a protein that contributes to lung scarring, suggesting potential benefits for treating this condition. ^{1 2 3 4 5}

Is EGCG safe for human consumption?

EGCG, a component of green tea, is generally considered safe for human consumption at doses below 600 mg per day, as no liver effects were observed in clinical studies at this level. However, high doses can cause liver toxicity, and a safe upper limit of 300 mg per day is recommended for supplements. Animal studies also suggest that EGCG is not genotoxic (does not damage genetic information) and has a no-observed adverse effect level of 500 mg/kg/day. ^{6 7 8 9 10}

How does the drug EGCG differ from other treatments for pulmonary fibrosis?

EGCG, a compound found in green tea, is unique because it acts as a strong antioxidant and anti-inflammatory agent, targeting specific pathways involved in lung fibrosis, such as the TGFβ1 signaling pathway. This makes it different from other treatments by potentially reducing inflammation and fibrosis through its antioxidant properties and modulation of cellular signaling. ^{1 3 5 8 11}

Research Team

Sydney Montesi, MD

Principal Investigator

Massachusetts General Hospital

Harold Chapman, MD

Principal Investigator

University of California, San Francisco

Fernando Martinez, MD

Principal Investigator

Cornell University

Eligibility Criteria

This trial is for adults aged 40-85 with idiopathic pulmonary fibrosis (IPF) who meet specific lung function criteria and have been on a stable dose of nintedanib or pirfenidone. They must not drink more than a cup of green tea daily, agree to birth control if applicable, and expect to live at least 9 months. Exclusions include certain medication use, other serious health conditions, recent infections or investigational therapies.

Inclusion Criteria

Agreement to refrain from drinking green tea in excess of a cup a day or eating green tea extract for 4 weeks before baseline and during the trial

I am between 40 and 85 years old.

I am a woman who can have children, tested negative for pregnancy, and will use birth control during the study.

Exclusion Criteria

I need oxygen or my oxygen levels are below 89% without it.

I haven't taken antibiotics for a lung infection in the last 4 weeks.

I have had hepatitis C or B, fatty liver disease, or cirrhosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral EGCG or placebo for 12 weeks, alongside standard IPF therapy with Nintedanib or Pirfenidone

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Epigallocatechin-3-gallate (EGCG) (Polyphenol)

Trial Overview The study tests the safety of EGCG from green tea in different doses combined with standard IPF treatments (nintedanib or pirfenidone) compared to placebo. It's a multi-center, double-blind trial meaning neither participants nor researchers know who gets the real treatment versus placebo.

Participant Groups

Group I: EGCG 600 mg with Nintedanib Active Control 1 Intervention

Patients enrolled in this group will be given oral capsule EGCG 600 mg daily with doctor provided Nintedanib for 12 weeks.

Group II: EGCG 600 mg with Pirfenidone Active Control 1 Intervention

Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks.

Group III: EGCG 300 mg with Pirfenidone Active Control 1 Intervention

Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Pirfenidone for 12 weeks.

Group IV: EGCG 300 mg with Nintedanib Active Control 1 Intervention

Patients enrolled in this group will be given oral capsule EGCG 300 mg daily with doctor provided Nintedanib for 12 weeks.

Group V: Placebo for EGCG 600 mg Placebo Group 1 Intervention

Patients enrolled in this group will be given oral capsule Placebo daily for 12 weeks with doctor provided Nintedanib or Pirfenidone. The number of placebo capsules will be equal to that of 600 mg EGCG.

Group VI: Placebo for EGCG 300 mg Placebo Group 1 Intervention

Patients enrolled in this group will be given oral capsule Placebo daily for 12 weeks with doctor provided Nintedanib or Pirfenidone. The number of placebo capsules will be equal to that of 300 mg EGCG.

Who Is Running the Clinical Trial?

Hal Chapman

Lead Sponsor

Trials

3

Recruited

110+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

James E. Ryan

University of Virginia

Chief Executive Officer since 2018

J.D. from Harvard Law School

Nikki Hastings

University of Virginia

Chief Medical Officer since 2018

Ph.D. in Biomedical Engineering from University of Virginia

Temple University

Collaborator

Trials

321

Recruited

89,100+

Dr. Kumar Budur

Temple University

Chief Medical Officer

MD, MS

Dr. Jeffrey M. Dayno

Temple University

Chief Executive Officer

MD from Temple University School of Medicine

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Marschall S. Runge

University of Michigan

Chief Executive Officer since 2015

MD, PhD

Karen McConnell

University of Michigan

Chief Medical Officer since 2020

MD

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

Matthew DeLisa

Cornell University

Chief Executive Officer since 2019

PhD in Chemical Engineering from Cornell University

Tami Magnus

Cornell University

Chief Medical Officer since 2015

MBA from Binghamton University

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

Findings from Research

In patients with Interstitial Lung Disease (ILD), the TGFβ1 signaling inhibitor epigallocatechin gallate (EGCG) effectively reduced harmful TGFβ1 signaling and inflammatory pathways in lung tissue, suggesting its potential as a therapeutic agent.

The study identified a novel mechanism where the fibroblast target gene sFRP2, influenced by TGFβ1 signaling, plays a crucial role in the trans-differentiation of alveolar epithelial cells, highlighting the complex interactions between fibroblasts and epithelial cells in lung diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fibroblast-dependent TGFβ1/sFRP2 noncanonical Wnt signaling axis underlies epithelial metaplasia in idiopathic pulmonary fibrosis. Cohen, ML., Brumwell, AN., Che Ho, T., et al.[2023]

In a rat model of irradiation-induced pulmonary fibrosis, treatment with epigallocatechin-3-gallate (EGCG) significantly reduced mortality rates and improved lung health compared to dexamethasone, indicating its potential as a safer alternative for treatment.

EGCG was found to activate the Nrf-2 pathway and enhance antioxidant enzyme levels, which contributed to its protective effects against lung fibrosis, suggesting a specific mechanism of action that could be beneficial in clinical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats. You, H., Wei, L., Sun, WL., et al.[2022]

(-)-Epigallocatechin-3-gallate (EGCG), a key component of green tea, acts as a powerful antioxidant and anti-inflammatory agent, showing potential benefits in treating various respiratory diseases by modulating oxidative stress and inflammation.

EGCG has been studied in multiple respiratory conditions, including COVID-19 and chronic obstructive pulmonary disease, suggesting its effectiveness in managing diseases characterized by inflammatory and fibrotic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases? Mokra, D., Adamcakova, J., Mokry, J.[2022]

A study tested the safety of Teavigo, a concentrated EGCG extract from green tea, and found no mutagenic activity in bacterial tests and no genotoxic effects in mouse bone marrow cells after various doses.

Oral and intravenous administration of EGCG did not induce harmful genetic changes, suggesting that Teavigo is safe for consumption and does not pose a genotoxic risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity. Isbrucker, RA., Bausch, J., Edwards, JA., et al.[2013]

Topical applications of high-concentration EGCG from green tea extract caused minor skin irritation in some animals, but overall, it was found to be relatively safe with a no-observed adverse effect level established at 500 mg/kg/day.

Oral administration of EGCG was lethal at very high doses (2000 mg/kg) in rats, but doses up to 500 mg/kg/day were safe over a 13-week period, indicating that while high doses can be toxic, moderate consumption is likely safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. Isbrucker, RA., Edwards, JA., Wolz, E., et al.[2022]

(-)-epigallocatechin gallate (EGCG), the main component of green tea, has been shown to inhibit the growth of human lung cancer cells, suggesting its potential as a cancer preventive agent.

Consuming over 10 cups of green tea daily was associated with a significant delay in cancer onset by 8.7 years for females and 3.0 years for males, highlighting the potential long-term benefits of green tea consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer inhibition by green tea. Fujiki, H., Suganuma, M., Okabe, S., et al.[2019]

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 involving pregnant rats, high-purity EGCG (Teavigo) showed no direct toxicity to embryos or fetuses at various doses during organ development, indicating potential safety for use during pregnancy.

However, while the highest doses did not harm reproduction or fertility, they did lead to reduced growth rates and increased pup loss, suggesting that careful dosing is important, with a no-observed adverse effect level (NOAEL) established at 200 mg/kg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Isbrucker, RA., Edwards, JA., Wolz, E., et al.[2022]

Cigarette smoke exposure in rats caused significant lung damage and increased oxidative stress, as evidenced by airspace enlargement and elevated serum 8-isoprostane levels after 56 days of exposure.

Consumption of Chinese green tea, rich in epigallocatechin-3-gallate (EGCG), effectively reversed the oxidative stress and lung damage caused by cigarette smoke, suggesting its protective role against lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats. Chan, KH., Ho, SP., Yeung, SC., et al.[2013]

References

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

A fibroblast-dependent TGFβ1/sFRP2 noncanonical Wnt signaling axis underlies epithelial metaplasia in idiopathic pulmonary fibrosis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats. [2022]

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

The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases? [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cancer inhibition by green tea. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats. [2013]