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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL142265 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This is a two part study. In the first part, the pharmacokinetic profile of Epigallocatechin-3-gallate (EGCG) in normal human volunteers given a single oral dose will be determined to set the dose for the second part of the study. In the second part of this study, lung biopsy fragments and urine samples from patients with interstitial lung disease treated with EGCG will be evaluated in biochemical assays and compared to samples from untreated control patients.
This is an interventional study intended to test inhibition of a signaling pathway in vivo in patients with interstitial lung disease, but not intended to affect lung function or disease modifications. Doses of oral Epigallocatechin-3-gallate (EGCG) that achieve plasma levels known to be safe in human volunteers and likely to target fibroblast TGFbeta RI kinase will be established. Disposable fragments of biopsies will be evaluated in biochemical assays including pSmad3 and Snail 1 or assayed to determine lysyl oxidase-like 2 (LOXL2) protein and LOXL2 enzyme activity. Urine collected before and after EGCG exposure will be used to determine whether terminal collagen cross-link breakdown products, termed pyridinoline/deoxypyridinoline (PYD/DPD) are changed from baseline. Blood collected before and after EGCG exposure will be assayed for serum biomarkers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EGCG PK in healthy volunteers 450 mg | Other | Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
|
| EGCG PK in healthy volunteers 600 mg | Other | Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
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| EGCG PK in healthy volunteers 750 mg | Other | Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
|
| No treatment control in ILD patients | No Intervention | Patients: not treated with EGCG | |
| EGCG treatment in ILD patients | Experimental | Patients: 600 mg EGCG capsules once daily by mouth for two weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epigallocatechin-3-gallate (EGCG) | Drug | Epigallocatechin-3-gallate (EGCG) capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| EGCG PK Level in Healthy Volunteers | EGCG plasma levels in healthy volunteers were measured at 0, 0.5, 2, and 4 hours after a single dose at 450 mg, 600 mg, or 750 mg dosage by liquid chromatography-mass spectrometry (LC-MS). | 0, 0.5, 2, 4 hours after EGCG |
| Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients | Change from baseline to day 14 in serum biomarkers associated with IPF, Cartilage Oligomeric Matrix Protein (COMP) measured by ELISA. | Day 1 to day 14 |
| Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients | Change from baseline to day 14 in serum biomarkers associated with IPF, Periostin measured by ELISA. | Day 1 to day 14 |
| Difference of Biomarker Snail1 Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker Snail1 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. | 14 days |
| Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker Collagen I in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. | 14 days |
| Difference of Biomarker p-Smad3 Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker p-Smad3 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hal A Chapman, MD | UC San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Francisco | San Francisco | California | 94143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33472968 | Background | Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney-Tait J, Cohen ML, Wolters PJ, Chapman HA. Blocking LOXL2 and TGFbeta1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. Thorax. 2021 Jul;76(7):729-732. doi: 10.1136/thoraxjnl-2020-215745. Epub 2021 Jan 20. | |
| 32160670 | Result | Chapman HA, Wei Y, Montas G, Leong D, Golden JA, Trinh BN, Wolters PJ, Le Saux CJ, Jones KD, Hills NK, Foster E, Oldham JM, Linderholm AL, Kotak P, Decaris M, Turner S, Song JW. Reversal of TGFbeta1-Driven Profibrotic State in Patients with Pulmonary Fibrosis. N Engl J Med. 2020 Mar 12;382(11):1068-1070. doi: 10.1056/NEJMc1915189. No abstract available. |
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Healthy volunteer recruitment started in 12/1/2017 and ended in 3/30/2018. Subjects were recruited from UCSF community. Advertisements were posted around the campus.
Patients recruitment started in 6/1/2018 and ended in 12/20/2018. Subjects were recruited from UCSF and UC Davis ILD clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | EGCG PK in Healthy Volunteers 450 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules) |
| FG001 | EGCG PK in Healthy Volunteers 600 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules) |
| FG002 | EGCG PK in Healthy Volunteers 750 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth (3 capsules) |
| FG003 | No Treatment Control in ILD Patients | None EGCG treated control ILD patients |
| FG004 | EGCG Treatment in ILD Patients | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Patients: 600 mg EGCG capsules once daily by mouth for two weeks (4 capsules once daily) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | EGCG PK in Healthy Volunteers 450 mg | Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 3 EGCG capsules |
| BG001 | EGCG PK in Healthy Volunteers 600 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | EGCG PK Level in Healthy Volunteers | EGCG plasma levels in healthy volunteers were measured at 0, 0.5, 2, and 4 hours after a single dose at 450 mg, 600 mg, or 750 mg dosage by liquid chromatography-mass spectrometry (LC-MS). | Posted | Mean | Standard Deviation | nM | 0, 0.5, 2, 4 hours after EGCG |
|
Adverse event data were collected during the whole course of the study (14 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EGCG PK in Healthy Volunteers 450 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
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The study was a pilot study with a small sample size.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Harold A. Chapman, M.D. | University of California at San Francisco | 415-514-1210 | hal.chapman@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 30, 2018 | Apr 27, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: Consent Form for ILD Patients | Jan 30, 2018 | Apr 27, 2022 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Consent Form for Healthy Volunteers | Jan 30, 2018 | Apr 27, 2022 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C045651 | epigallocatechin gallate |
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Open Label
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| 14 days |
Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 4 EGCG capsules |
| BG002 | EGCG PK in Healthy Volunteers 750 mg | Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Epigallocatechin-3-gallate (EGCG): 5 EGCG capsules |
| BG003 | No Treatment Control in ILD Patients | ILD patients that were not treated with EGCG are used as controls. |
| BG004 | EGCG Treatment in ILD Patients | Patients: 600 mg EGCG capsules once daily by mouth for two weeks Epigallocatechin-3-gallate (EGCG): 4 EGCG capsules |
| BG005 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| High-resolution computed tomography (HRCT) imaging indicative of lung fibrosis | Count of Participants | Participants |
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| OG002 | EGCG PK in Healthy Volunteers 750 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
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| Primary | Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients | Change from baseline to day 14 in serum biomarkers associated with IPF, Cartilage Oligomeric Matrix Protein (COMP) measured by ELISA. | Serum biomarker COMP was measured by ELISA and compared before and after EGCG treatment. | Posted | Mean | Standard Deviation | ng/ml | Day 1 to day 14 |
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| Primary | Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients | Change from baseline to day 14 in serum biomarkers associated with IPF, Periostin measured by ELISA. | Serum biomarker Periostin was measured by ELISA and compared before and after EGCG treatment. | Posted | Mean | Standard Deviation | ng/ml | Day 1 to day 14 |
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| Primary | Difference of Biomarker Snail1 Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker Snail1 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. | Posted | Mean | Standard Deviation | percentage of reference sample | 14 days |
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| Primary | Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker Collagen I in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. | Posted | Mean | Standard Deviation | percentage of reference sample | 14 days |
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| Primary | Difference of Biomarker p-Smad3 Between EGCG-treated and Non-treated Patient Groups | Levels of biomarker p-Smad3 in lung biopsy tissues 14 days after EGCG were measured by western blot and differences were compared between EGCG-treated and non-treated groups. | Posted | Mean | Standard Deviation | percentage of reference sample | 14 days |
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| 0 |
| 5 |
| 0 |
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| 0 |
| 5 |
| EG001 | EGCG PK in Healthy Volunteers 600 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth | 0 | 5 | 0 | 5 | 0 | 5 |
| EG002 | EGCG PK in Healthy Volunteers 750 mg | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth | 0 | 5 | 0 | 5 | 0 | 5 |
| EG003 | No Treatment Control in ILD Patients | ILD patients that were not treated with EGCG are used as controls. | 0 | 10 | 0 | 10 | 0 | 10 |
| EG004 | EGCG Treatment in ILD Patients | Teavigo EGCG capsule containing 94% EGCG, 150 mg EGCG/capsule Patients: 600 mg EGCG capsules once daily by mouth for two weeks (4 capsules once daily) | 0 | 10 | 0 | 10 | 0 | 10 |
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