EGCG for Pulmonary Fibrosis

Recruiting at 7 trial locations

Overseen By Harold Chapman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hal Chapman

Must be taking: Nintedanib, Pirfenidone

Must not be taking: Corticosteroids, Digoxin

Disqualifiers: HCV, HBV, Emphysema, Alcohol, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for idiopathic pulmonary fibrosis (IPF), a disease that causes lung scarring and breathing problems. Researchers are testing the safety of Epigallocatechin-3-gallate (EGCG), a compound from green tea, combined with existing medications, to determine its effectiveness in managing IPF. Participants will receive either different doses of EGCG with standard treatments or a placebo (a pill with no active ingredient). The trial seeks individuals with IPF who have consistently taken either nintedanib or pirfenidone for at least 12 weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Epigallocatechin-3-gallate (EGCG), a compound in green tea, is under study for its safety in humans. Previous studies found that people generally tolerated EGCG well. However, since this trial is in the early stages, researchers are still gathering detailed safety information. While early results appear promising, more data is needed to fully understand any potential side effects or risks of EGCG. EGCG is being tested with other medications like Nintedanib and Pirfenidone, which have established safety records. Researchers will closely monitor participants to ensure their safety as they continue to learn how EGCG affects patients with idiopathic pulmonary fibrosis, a lung disease that causes scarring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Epigallocatechin-3-gallate (EGCG) for pulmonary fibrosis because it introduces a natural compound found in green tea with potential anti-fibrotic properties. Unlike standard treatments like Nintedanib and Pirfenidone, which primarily focus on slowing disease progression, EGCG may offer a novel way to combat fibrosis by targeting oxidative stress and inflammation at the cellular level. This unique mechanism of action sets EGCG apart, as it may complement existing therapies with its potential to modify the disease process itself.

What evidence suggests that EGCG might be an effective treatment for pulmonary fibrosis?

Studies have shown that EGCG, a compound in green tea, might help with idiopathic pulmonary fibrosis (IPF). Research suggests that EGCG can prevent collagen buildup in the lungs, a major issue in fibrosis. In lab studies with mice, EGCG reduced lung scarring by blocking certain cell activities that cause fibrosis. Although human studies provide limited information, these early results are promising for EGCG's potential in treating IPF. This trial will evaluate the effects of EGCG combined with either Nintedanib or Pirfenidone, as well as a placebo group, to further explore its potential benefits for IPF patients. ^{1 2 3 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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

I am between 40 and 85 years old.

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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Epigallocatechin-3-gallate (EGCG)

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.

How Is the Trial Designed?

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.

Epigallocatechin-3-gallate (EGCG) is already approved in United States for the following indications:

Approved in United States as Epigallocatechin gallate for:

• Investigational for Hypertension and Diabetic Nephropathy
• Potential novel treatment for pulmonary fibrosis

Who Is Running the Clinical Trial?

Hal Chapman

Lead Sponsor

Trials

3

Recruited

110+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Temple University

Collaborator

Trials

321

Recruited

89,100+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

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]

(-)-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]

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]

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]

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 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]

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]

Epigallocatechin gallate (EGCG) has been identified as a dual inhibitor of key pathways involved in fibrosis, showing promise in reversing profibrotic biomarkers in patients with idiopathic pulmonary fibrosis (IPF).

In advanced pulmonary fibrosis models, EGCG not only reduced TGFβ1 signaling and collagen buildup but also promoted the turnover of collagen I, suggesting it may help in the gradual resolution of fibrosis with ongoing treatment.

NCBI (Pubmed)

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. Wei, Y., Dong, W., Jackson, J., et al.[2022]

(-)-epigallocatechin-3-gallate (EGCG) effectively inhibits cell proliferation in non-small cell lung cancer (NSCLC) cell lines, including those resistant to the EGFR antagonist erlotinib, suggesting its potential as a treatment option.

The combination of EGCG with erlotinib and the c-Met inhibitor SU11274 showed enhanced anti-cancer effects, indicating that EGCG could be a valuable adjunct therapy alongside existing treatments for NSCLC.

NCBI (Pubmed)

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. Milligan, SA., Burke, P., Coleman, DT., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6514693/

The Effects of Epigallocatechin Gallate (EGCG) on ... Idiopathic pulmonary fibrosis (IPF) is a disabling and lethal chronic progressive pulmonary disease. Epigallocatechin gallate (EGCG) is a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05195918

Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF ... The rationale for this study is 1) extensive pre-clinical data in mice that EGCG is efficacious in attenuating pulmonary fibrosis by blocking collagen cross- ...

3. jci.org jci.org/articles/view/183970

epigallocatechin gallate targets fibroblast–epithelial cell ... This study emphasizes the epithelial-mesenchymal trophic unit as a central signaling hub in lung fibrosis. Understanding and simultaneous ...

4. pulmonaryfibrosis.org pulmonaryfibrosis.org/patients-caregivers/medical-and-support-resources/find-medical-care/care-center-new/NCT05195918-1576838

Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF ... Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S135727251930189X

Epigallocatechin-3-gallate (EGCG) inhibits aggregation of ... Epigallocatechin-3-gallate (EGCG) inhibits aggregation of pulmonary fibrosis associated mutant surfactant protein A2 via a proteasomal degradation pathway.

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05195918

Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients The study will assess safety, pharmacokinetics, and biomarker measurements of drug effect in IPF patients already receiving background therapy ...

7. pulmonaryfibrosis.org pulmonaryfibrosis.org/patients-caregivers/medical-and-support-resources/clinical-trials-education-center/pipeline/drug/idiopathic-pulmonary-fibrosis/epigallocatechin-3-gallate

Epigallocatechin-3-gallate The primary purpose of this multi-center, double-blind, placebo-controlled, dose-ranging Phase I study is to assess the safety of a purified from green tea, ...