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

Trial Summary

What is the purpose of this trial?

The primary purpose of this substudy is to determine if collagen-targeted PET using the type 1 collagen-targeted PET probe, Gallium-68 (68Ga)-labeled collagen binding probe 8 (CBP8) can inform as to drug effect of EGCG and assist in dose selection.

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.

What data supports the effectiveness of the treatment 68Ga-CBP8 for pulmonary fibrosis?

Research shows that 68Ga-CBP8, a probe that targets collagen, is effective in detecting and monitoring pulmonary fibrosis in animal models. It has shown high specificity for lung scarring and correlates well with the amount of lung collagen, making it a promising tool for noninvasive imaging of pulmonary fibrosis in humans. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Gallium-68 (68Ga)-labeled collagen binding probe 8 (CBP8) for pulmonary fibrosis?

Research shows that 68Ga-CBP8 is effective in detecting and monitoring pulmonary fibrosis in animal models, with high specificity for lung scarring and a strong correlation between probe uptake and lung collagen levels. Additionally, studies in humans indicate that 68Ga-CBP8 is safe and could be used for noninvasive imaging of fibrotic diseases. ^{1 2 3 4 5}

Is 68Ga-CBP8 safe for use in humans?

In a study with nine healthy volunteers, 68Ga-CBP8 was found to be safe with no adverse effects reported. It showed rapid clearance from the body, mainly through the kidneys, and had a safety profile similar to other gallium-based probes. ^{1 2 3 4 5}

Is 68Ga-CBP8 safe for use in humans?

In a study with nine healthy volunteers, 68Ga-CBP8 was found to be safe with no adverse effects reported. It showed rapid clearance from the body, mainly through the kidneys, and had a safety profile similar to other gallium-based probes. ^{1 2 3 4 5}

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

EGCG, a component of green tea, is unique because it binds to specific proteins involved in cell adhesion, potentially reducing fibrosis by preventing cells from sticking to fibronectin, a protein that contributes to tissue scarring. This mechanism is different from other treatments that may not target cell adhesion directly. ^{1 2 5 6 7}

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

EGCG, a component of green tea, is unique because it targets the 67 kDa laminin receptor, which is different from other treatments for pulmonary fibrosis that typically focus on reducing inflammation or fibrosis directly. This novel mechanism may offer a new approach to managing the condition. ^{1 2 5 6 7}

Research Team

Fernando Martinez, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

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

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. [2018]

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

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. [2023]

3. Austria pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. [2021]

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

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. [2020]

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

A gold-complex initiated functionalization of biologically active polyphenols applied to a 18F-labeled chemical probe. [2023]

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

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