EGCG for Pulmonary Fibrosis
Palo Alto (17 mi)Overseen byHarold Chapman, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Hal Chapman
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.
Is the drug EGCG a promising treatment for pulmonary fibrosis?Yes, EGCG, a compound found in green tea, shows promise as a treatment for pulmonary fibrosis. It acts as a strong antioxidant, reduces inflammation, and helps prevent lung tissue damage. Studies suggest it can improve lung health by reducing harmful processes in the lungs.1571011
What safety data exists for EGCG treatment?EGCG, a component of green tea, has been studied for safety in various contexts. Genotoxicity studies show no mutagenic activity in bacterial systems and no genotoxic effects in mice and rats at tested doses. Dermal and acute toxicity studies indicate minor irritation and a no-observed adverse effect level (NOAEL) of 500 mg/kg/day in rats and dogs. High doses can be lethal, but lower doses are non-toxic. EGCG is not associated with liver damage in humans at typical consumption levels, with a proposed tolerable upper intake level of 300 mg/person/day for supplements. Reproductive studies in rats show no adverse effects on reproduction or fetal development at certain doses, with a NOAEL of 200 mg/kg/day during lactation.12348
What data supports the idea that EGCG for Pulmonary Fibrosis is an effective treatment?The available research shows that EGCG, a compound found in green tea, can help treat pulmonary fibrosis by reducing harmful signals in the lungs and promoting the breakdown of excess collagen, which is a protein that builds up in this disease. In studies with lung tissue from patients, EGCG was found to reverse some of the harmful changes associated with pulmonary fibrosis. Additionally, in animal studies, EGCG reduced the severity of lung damage and inflammation. Compared to other treatments, EGCG not only reduces harmful signals but also helps clear out excess collagen, suggesting it might be a promising option for managing pulmonary fibrosis.6791011
Do I need to stop my current medications to join the trial?The trial requires that you have been on a stable dose of nintedanib or pirfenidone for at least 12 weeks before starting. You cannot be on digoxin or systemic corticosteroids above a certain dose. The protocol does not specify other medications, so check with the trial team for more details.
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
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.
I can take pills and will follow the EGCG treatment plan.
My lung function is at least half of what is expected for someone my age and size.
I have been diagnosed with IPF according to the 2022 ATS criteria.
Exclusion Criteria
I need oxygen or my oxygen levels are below 89% without it.
I have had hepatitis C or B, fatty liver disease, or cirrhosis.
I am taking more than 10 mg/day of corticosteroids or its equivalent.
I am currently taking digoxin and will continue to do so during the study.
Treatment Details
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.
6Treatment groups
Active Control
Placebo Group
Group I: EGCG 600 mg with NintedanibActive Control1 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 PirfenidoneActive Control1 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 PirfenidoneActive Control1 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 NintedanibActive Control1 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 mgPlacebo Group1 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 mgPlacebo Group1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
Weill Cornell MedicineNew York, NY
Temple UniversityPhiladelphia, PA
University of VirginiaCharlottesville, VA
More Trial Locations
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Who is running the clinical trial?
Hal ChapmanLead Sponsor
University of VirginiaCollaborator
Temple UniversityCollaborator
University of MichiganCollaborator
Cornell UniversityCollaborator
Massachusetts General HospitalCollaborator
University of WashingtonCollaborator
References
Cancer inhibition by green tea. [2019]Green tea is now an acknowledged cancer preventive in Japan. This paper discusses several important features of (-)-epigallocatechin gallate (EGCG), the main constituent of green tea and tea polyphenols. EGCG and other tea polyphenols inhibited growth of human lung cancer cell line, PC-9 cells with G2/M arrest. 3H-EGCG administered by p.o. intubation into mouse stomach revealed that small amounts of 3H-activity were found in various organs where EGCG and green tea extract had previously demonstrated their anticarcinogenic effects, such as skin, stomach, duodenum, colon, liver, lung and pancreas. Cancer onset of patients who had consumed over 10 cups of green tea per day was 8.7 years later among females and 3.0 years later among males, compared with patients who had consumed under three cups per day. The mechanisms of action of EGCG were briefly discussed with regard to inhibition of tumor necrosis factor-alpha (TNF-alpha) release.
Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity. [2013]Public interest in green tea has grown recently due to the potential health benefits from its consumption. Epigallocatechin gallate (EGCG), a principal polyphenolic component of green tea, is considered key to these healthful qualities. Although numerous studies have evaluated the anti-cancer effects of green tea and EGCG, few have examined the safety of EGCG consumption. The genotoxic potential of a concentrated EGCG preparation was tested in Salmonella and L5178Y tk+/- mouse lymphoma cell assays to further define the safety of Teavigo, a high-concentration EGCG extract of Camellia sinensis leaves produced by the same novel method. No mutagenic activity was detected in the bacterial system; however, a clastogenic 'trend' from the formation of hydrogen peroxide was noted in the murine cells. The oral administration of 500, 1000, or 2000 mg EGCG/kg to mice did not induce micronuclei formation in bone marrow cells. Similarly, administering 400, 800, or 1200 mg EGCG/kg/day in their diet for 10 days did not induce bone marrow cell micronuclei and produced plasma EGCG concentrations comparable to those reported in human studies. The intravenous injection of 10, 25 and 50 mg EGCG/kg/day to rats resulted in much higher plasma concentrations and demonstrated an absence of genotoxic effects. From these studies, it is concluded that Teavigo (EGCG) is not genotoxic.
Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. [2022]Green tea extract and its principal active ingredient, epigallocatechin gallate (EGCG), are gaining attention and increased usage due to their healthful properties. Despite the increasing demand for these products, few studies have examined their safety. The toxicity of purified green tea extracts containing high concentrations of EGCG have been evaluated in a series of studies in order to define the safety of Teavigo, a high-concentration EGCG extract produced by the same novel method. Topical EGCG preparations caused minor dermal irritation in rats and guinea pigs, but not rabbits, and was a moderate dermal sensitizing agent in the guinea pig maximization test. A rabbit eye irritation test produced a strong enough response to not warrant any further testing in this assay. An oral dose delivering 2000 mg EGCG preparation/kg was lethal to rats; whereas, a dose of 200 mg EGCG/kg induced no toxicity. The dietary administration of EGCG preparation to rats for 13 weeks was not toxic at doses up to 500 mg/kg/day. Similarly, no adverse effects were noted when 500 mg EGCG preparation/kg/day was administered to pre-fed dogs in divided doses. This dose caused morbidity when administered to fasted dogs as a single bolus dose, although this model was considered an unrealistic comparison to the human condition. From these studies a no-observed adverse effect level of 500 mg EGCG preparation/kg/day was established.
Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. [2022]Green tea and its principal active ingredient, epigallocatechin gallate (EGCG), have been demonstrated to have anticancer properties through interactions with multiple biochemical processes. Since these processes are often crucial in normal fetal development it is important to evaluate the potential effects of EGCG on the fetus. EGCG preparations of >91% purity were administered to pregnant rats during organogenesis and development in order to define the safety of Teavigo, a high-concentration EGCG extract produced by the same novel method. In an initial preliminary study using subcutaneous and gavage routes, there was no evidence of any direct embryo-fetal toxicity, although some maternal toxicity was seen. In the main teratogenicity study, feeding pregnant rats diets supplemented at 1400, 4200 or 14,000 ppm during organogenesis was non-toxic to dams or fetuses. A two-generation study in rats fed 1200, 3600 or 12,000 ppm EGCG preparation showed no adverse effects on reproduction or fertility. The highest dose reduced the growth rate of offspring, and there was a slight increase in pup loss. A growth effect among pups was also seen at 3600 ppm, but in the second generation only. The lowest dose was considered the overall no-observed adverse effect level (NOAEL). As dams consumed twice the amount of feed during the crucial lactation period, the NOAEL was equivalent to 200 mg/kg/day EGCG preparation.
Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats. [2013]Epigallocatechin-3-gallate (EGCG), which has been shown to have potent antioxidant effect, comprises 80% of catechins in Chinese green tea. This study was to investigate whether cigarette smoke (CS) exposure would induce lung morphological changes and oxidative stress in the CS-exposed rat model, and whether Chinese green tea (Lung Chen tea with EGCG as its main active ingredient) consumption would alter oxidative stress in sera and lung leading to protection of CS-induced lung damage.
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]Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non-small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines.
The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats. [2022]The present study evaluated the effect of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, on irradiation-induced pulmonary fibrosis and elucidated its mechanism of action. A rat model of irradiation-induced pulmonary fibrosis was generated using a (60)Co irradiator and a dose of 22 Gy. Rats were intraperitoneally injected with EGCG (25 mg/kg) or dexamethasone (DEX; 5 mg/kg) daily for 30 days. Mortality rates and lung index values were calculated. The severity of fibrosis was evaluated by assaying the hydroxyproline (Hyp) contents of pulmonary and lung tissue sections post-irradiation. Alveolitis and fibrosis scores were obtained from semi-quantitative analyses of hematoxylin and eosin (H&E) and Masson's trichrome lung section staining, respectively. The serum levels of transforming growth factor β1 (TGF-β1), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) were also measured. Surfactant protein-B (SPB) and α-SMA expression patterns were evaluated using immunohistochemistry, and the protein levels of nuclear transcription factor NF-E2-related factor 2 (Nrf-2) and its associated antioxidant enzymes heme oxygenase-1 enzyme (HO-1) and
Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements. [2017]The safety of green tea infusions and green tea extract (GTE)-based products is reviewed regarding catechins. Epigallocatechin 3-gallate (EGCG), the major catechin present in green tea, is suspected of being responsible for liver toxicity reported in humans consuming food supplements. Intake of EGCG with green tea infusions and GTE-based beverages is up to about 450mg EGCG/person/day in Europe and higher in Asia. Consumption of green tea is not associated with liver damage in humans, and green tea infusion and GTE-based beverages are considered safe in the range of historical uses. In animal studies, EGCG's potency for liver effects is highly dependent on conditions of administration. Use of NOAELs from bolus administration to derive a tolerable upper intake level applying the margin of safety concept results in acceptable EGCG-doses lower than those from one cup of green tea. NOAELs from toxicity studies applying EGCG with diet/split of the daily dose are a better point of departure for risk characterization. In clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day. Thus, a tolerable upper intake level of 300mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects and a margin of safety of 100 to the NOAELs in animal studies with dietary administration of green tea catechins.
Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. [2022]We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-β1 (TGFβ1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFβ1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.
Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases? [2022](-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that possesses a wide variety of actions. EGCG acts as a strong antioxidant which effectively scavenges reactive oxygen species (ROS), inhibits pro-oxidant enzymes including NADPH oxidase, activates antioxidant systems including superoxide dismutase, catalase, or glutathione, and reduces abundant production of nitric oxide metabolites by inducible nitric oxide synthase. ECGC also exerts potent anti-inflammatory, anti-fibrotic, pro-apoptotic, anti-tumorous, and metabolic effects via modulation of a variety of intracellular signaling cascades. Based on this knowledge, the use of EGCG could be of benefit in respiratory diseases with acute or chronic inflammatory, oxidative, and fibrotizing processes in their pathogenesis. This article reviews current information on the biological effects of EGCG in those respiratory diseases or animal models in which EGCG has been administered, i.e., acute respiratory distress syndrome, respiratory infections, COVID-19, bronchial asthma, chronic obstructive pulmonary disease, lung fibrosis, silicosis, lung cancer, pulmonary hypertension, and lung embolism, and critically discusses effectiveness of EGCG administration in these respiratory disorders. For this review, articles in English language from the PubMed database were used.
A fibroblast-dependent TGFβ1/sFRP2 noncanonical Wnt signaling axis underlies epithelial metaplasia in idiopathic pulmonary fibrosis. [2023]Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate this, we administered the fibroblast-selective TGFβ1 signaling inhibitor, epigallocatechin gallate (EGCG), to Interstitial Lung Disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA sequencing on spare tissue. Unexposed biopsy samples showed higher fibroblast TGFβ1 signaling compared to non-disease donor or end-stage ILD tissues. In vivo, EGCG significantly downregulated TGFβ1 signaling and several pro-inflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted Frizzle-like Receptor Protein 2 (sFRP2), an unrecognized TGFβ1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s). In human AEC2-fibroblast coculture organoids, sFRP2 was essential for AEC2 trans-differentiation to basal cells. Precision cut lung slices (PCLS) from normal donors demonstrated that TGFβ1 promoted KRT17 expression and AEC2 morphological change, while sFRP2 was necessary for KRT5 expression in AEC2-derived basaloid cells. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin-related signaling in AEC2s were required for sFRP2-induced KRT5 expression. These findings highlight stage-specific TGFβ1 signaling in ILD, the therapeutic potential of EGCG in reducing IPF-related transcriptional changes, and identify the TGFβ1-non-canonical Wnt pathway crosstalk via sFRP2 as a novel mechanism for dysfunctional epithelial signaling in Idiopathic Pulmonary Fibrosis/ILD.