EGCG for Pulmonary Fibrosis

Recruiting at 2 trial locations

Overseen By Sydney Montesi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hal Chapman

Disqualifiers: Pregnancy, Radiation exposure, Implants, Claustrophobia, Low eGFR, others

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to evaluate the effectiveness of a treatment called EGCG for Idiopathic Pulmonary Fibrosis (IPF), a lung disease that causes scarring. Researchers aim to determine if a special imaging technique can reveal the effects of EGCG, administered in varying doses to compare its impact. Participants will receive either an active dose of EGCG or a placebo (a pill with no active drug) alongside their usual anti-fibrotic medication. Individuals diagnosed with IPF and currently on medication may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention evaluating interactions with standard care drugs, so it's best to discuss your current medications with the trial team.

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

The trial information does not specify if you need to stop your current medications. However, it mentions evaluating interactions with standard care drugs, so it's best to discuss this with the trial team.

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

Research has shown that EGCG, a compound in green tea, is generally well-tolerated. One study examined its use in people with idiopathic pulmonary fibrosis (IPF), a lung disease, and found that EGCG was safe for these patients, even those already on other IPF medications.

Participants in previous studies did not report any serious side effects from taking EGCG, suggesting that the treatment is likely safe for humans. However, some individuals might experience mild side effects like an upset stomach or headaches, which are common when trying new substances.

Overall, while earlier studies suggest EGCG is safe, anyone considering a clinical trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Researchers are excited about using EGCG for pulmonary fibrosis because it offers a natural, plant-derived alternative to traditional treatments. EGCG, a compound found in green tea, is believed to have anti-fibrotic properties that could help slow down or even reverse lung damage. Unlike standard treatments like pirfenidone or nintedanib, which primarily work by inhibiting pathways leading to fibrosis, EGCG may offer a new mechanism of action by directly interacting with the processes involved in tissue scarring. This novel approach could provide additional benefits and options for patients with pulmonary fibrosis.

What evidence suggests that this trial's treatments could be effective for pulmonary fibrosis?

Research has shown that Epigallocatechin Gallate (EGCG), a compound found in tea, may help treat pulmonary fibrosis, a lung condition. Studies have found that EGCG can reduce the production of TNF-α, a molecule that causes inflammation and may worsen this condition. In animal studies, EGCG decreased lung scarring by preventing the hardening of collagen, which is important in the development of fibrosis. Additionally, EGCG can change the activity of certain genes in lung cells, potentially reducing fibrosis. These findings suggest that EGCG has promising properties for reducing lung scarring. In this trial, participants will receive either EGCG at doses of 300 mg or 600 mg, or a placebo, to evaluate its effectiveness in treating pulmonary fibrosis. ^{1 2 6 7 8}

Who Is on the Research Team?

Fernando Martinez, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for individuals with Pulmonary Fibrosis or Idiopathic Pulmonary Fibrosis. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and may be required to have a confirmed diagnosis of the conditions mentioned.

Inclusion Criteria

Enrolled in and eligible for the main EGCG Phase 1 study

Signed informed consent

Exclusion Criteria

My kidney function test shows an eGFR below 30.

Pregnant or breastfeeding (a negative quantitative serum human chorionic gonadotropin (hCG) pregnancy test is required for females having child-bearing potential before participation)

Research-related radiation exposure exceeds 50 millisievert (mSv) in the prior 12 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive oral EGCG or placebo daily for 12 weeks with doctor-provided anti-fibrotic treatment

12 weeks

2 visits (in-person) for PET scans

PET Imaging

Participants undergo [68Ga]CBP8 PET-CT or PET-MRI to assess collagen deposition

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gallium-68 (68Ga)-labeled collagen binding probe 8 (CBP8)

Trial Overview The study is testing the effects of EGCG at two different doses (300 mg and 600 mg) compared to placebos. It uses a PET imaging probe called Gallium-68 (68Ga)-CBP8 to see if it can show how well EGCG works in treating fibrosis and help choose the right dose.

How Is the Trial Designed?

Group I: EGCG 300 mg Active Control 2 Interventions

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

Group II: EGCG 600 mg Active Control 2 Interventions

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

Group III: Placebo for EGCG 300 mg Placebo Group 2 Interventions

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

Group IV: Placebo for EGCG 600 mg Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Hal Chapman

Lead Sponsor

Trials

3

Recruited

110+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

The 68Ga-Collagen Binding Probe #8 (68Ga-CBP8) was safely administered to nine healthy volunteers, showing no adverse effects and demonstrating favorable biodistribution with rapid renal clearance.

This probe has potential for noninvasive imaging of tissue fibrosis, with pharmacokinetics indicating a quick initial distribution and a longer elimination phase, making it suitable for assessing fibrotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. Izquierdo-Garcia, D., Désogère, P., Fur, ML., et al.[2023]

An improved collagelin analogue labeled with gallium-68 for PET imaging shows promise for non-invasive and sensitive assessment of fibrosis, achieving a high radiochemical purity of 98% and stable performance for at least 3 hours.

In studies with mice, the new imaging agent demonstrated specific binding to fibrotic liver tissue, correlating well with fibrosis severity, and exhibited a safe dosimetry profile allowing for multiple PET scans per year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. Velikyan, I., Rosenström, U., Rosestedt, M., et al.[2021]

CBP1495 is a newly identified collagen-binding peptide that effectively targets collagen type I, showing strong binding affinity and potential for use in imaging fibrosis.

The 99mTc-labelled version of CBP1495 demonstrated significant accumulation in fibrotic tissues in rat models, indicating its potential as a non-invasive radiotracer for diagnosing and monitoring fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. Zheng, L., Ding, X., Liu, K., et al.[2018]

The peptide-based PET probe 68Ga-CBP8 specifically targets collagen type I and shows high specificity for pulmonary fibrosis in a mouse model, indicating its potential for noninvasive imaging of this condition.

In vivo and ex vivo studies demonstrated a strong correlation between 68Ga-CBP8 uptake and lung collagen levels, suggesting it could effectively monitor treatment responses in pulmonary fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Désogère, P., Tapias, LF., Hariri, LP., et al.[2018]

The study developed a collagen-targeted PET probe, 64Cu-CBP7, which showed significantly higher uptake in the lungs of mice with bleomycin-induced pulmonary fibrosis compared to healthy controls, indicating its potential for early detection of lung fibrosis.

64Cu-CBP7 demonstrated superior metabolic stability and specificity for collagen, making it a promising candidate for noninvasive imaging of pulmonary fibrosis progression in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. Désogère, P., Tapias, LF., Rietz, TA., et al.[2020]

The study successfully modified the A ring of (-)-Epigallocatechin gallate (EGCG) to create new drug candidates, demonstrating that these modifications do not compromise EGCG's anticancer efficacy in U266 cells.

The research also achieved the synthesis of 18F-labeled EGCG, with promising radiochemical yields, indicating potential for developing new imaging and therapeutic agents using EGCG as a base.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A gold-complex initiated functionalization of biologically active polyphenols applied to a 18F-labeled chemical probe. Liu, Z., Fukagawa, Y., Yamano, M., et al.[2023]

(-)-Epigallocatechin gallate (EGCg) inhibits lung carcinoma cell adhesion to fibronectin (FN) by interacting with a specific fragment of FN, identified as a carboxyl-terminal heparin-binding domain.

This study reveals that EGCg's mechanism of action does not involve direct binding to the cell-binding domain of FN, suggesting a more complex interaction that could inform future cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between the carboxyl-terminal heparin-binding domain of fibronectin and (-)-epigallocatechin gallate. Sazuka, M., Isemura, M., Isemura, S.[2013]

Citations

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

The Effects of Epigallocatechin Gallate (EGCG) on ... EGCG has been shown to inhibit the production of TNF-α, which might play an important role in the pathogenesis of IPF [41]. Sriram et al. have ...

2. jci.org jci.org/articles/view/183970

epigallocatechin gallate targets fibroblast–epithelial cell ... Epigallocatechin gallate (EGCG) is a polyphenol plant metabolite abundant in tea that has demonstrated antifibrotic properties in the lung.

3. 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- ...

4. atsjournals.org atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A7424?download=true

The Possible Effects of Epigallocatechin Gallate on ... Results: A total of 45 significantly upregulated and 16 significantly downregulated genes were found in EGCG-treated versus control fibroblasts, ...

5. spandidos-publications.com spandidos-publications.com/10.3892/ijmm.2014.1745

International Journal of Molecular Medicine Taken together, these results showed that EGCG treatment significantly inhibits irradiation-induced pulmonary fibrosis. Furthermore, the results ...

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. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/327615

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

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

Epigallocatechin-3-gallate (EGCG) inhibits aggregation of ... In summary, this study demonstrated that EGCG significantly reduced aggregation of mutant SP-A2 protein (G231V, F198S), associated with pulmonary fibrosis, by ...