Idiopathic Pulmonary FibrosisEarly Phase 1NCT03928847
Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.
A Early Phase 1 study testing Epigallocatechin-3-gallate (EGCG) in people with Idiopathic Pulmonary Fibrosis, run by Hal Chapman at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Epigallocatechin-3-gallate (EGCG)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2017to 31 May 2019
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Part 1: healthy volunteers
- Part 2:
- study will consist of patients presenting to the UCSF interstitial lung disease (ILD) outpatient clinic with imaging indicative of lung fibrosis but of uncertain classification, and who are willing to take EGCG for a minimum of 2 weeks prior to surgery.
Who cannot join
- co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
- using drugs with significant hepatic toxicities
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- Epigallocatechin-3-gallate (EGCG)
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epigallocatechin-3-gallate (EGCG)Drug
Also called Teavigo
Epigallocatechin-3-gallate (EGCG) capsules
| Study group | Role | What they receive |
|---|---|---|
| EGCG PK in healthy volunteers 450 mg | Other | Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Receives: Drug: Epigallocatechin-3-gallate (EGCG) |
| EGCG PK in healthy volunteers 600 mg | Other | Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Receives: Drug: Epigallocatechin-3-gallate (EGCG) |
| EGCG PK in healthy volunteers 750 mg | Other | Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth Receives: Drug: Epigallocatechin-3-gallate (EGCG) |
| 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 Receives: Drug: Epigallocatechin-3-gallate (EGCG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start1 Dec 2017
- Primary completion31 May 2019
- Study completion31 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hal Chapman
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Hal Chapman, University of California, San Francisco
- Investigators
- Hal A Chapman, MD, Principal investigator, UC San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928847
- Sponsor's protocol ID
- 17-23008
- Other IDs
- R01HL142265
- Status last verified
- Dec 2022
- First submitted
- 18 Apr 2019
- Last updated
- 22 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33472968Chapman 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.
PubMed 32160670
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.
- ClinicalTrials.gov ID
- NCT03928847
- Acronym / sponsor ID
- 17-23008
- Conditions
- Idiopathic Pulmonary Fibrosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Hal ChapmanUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 31 May 2019 (actual)
- First posted
- 26 Apr 2019 (actual)
- Results
- Posted 22 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| EGCG PK in healthy volunteers 450 mg | Other | Drug: Epigallocatechin-3-gallate (EGCG)Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
| EGCG PK in healthy volunteers 600 mg | Other | Drug: Epigallocatechin-3-gallate (EGCG)Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth |
| EGCG PK in healthy volunteers 750 mg | Other | Drug: Epigallocatechin-3-gallate (EGCG)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 | Drug: Epigallocatechin-3-gallate (EGCG)Patients: 600 mg EGCG capsules once daily by mouth for two weeks |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Part 1: healthy volunteers
- Part 2:
- study will consist of patients presenting to the UCSF interstitial lung disease (ILD) outpatient clinic with imaging indicative of lung fibrosis but of uncertain classification, and who are willing to take EGCG for a minimum of 2 weeks prior to surgery.
Key exclusion criteria (2 listed)
- co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
- using drugs with significant hepatic toxicities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epigallocatechin-3-gallate (EGCG)Also: TeavigoEpigallocatechin-3-gallate (EGCG) capsules | Drug | EGCG PK in healthy volunteers 450 mg, EGCG PK in healthy volunteers 600 mg, EGCG PK in healthy volunteers 750 mg, EGCG treatment in ILD patients |
Primary outcome
EGCG PK Level in Healthy Volunteers
Time frame: 0, 0.5, 2, 4 hours after EGCG
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).
Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients
Time frame: Day 1 to day 14
Change from baseline to day 14 in serum biomarkers associated with IPF, Cartilage Oligomeric Matrix Protein (COMP) measured by ELISA.
Change of Serum Biomarker Periostin Before and After EGCG Treatment in ILD Patients
Time frame: Day 1 to day 14
Change from baseline to day 14 in serum biomarkers associated with IPF, Periostin measured by ELISA.
Difference of Biomarker Snail1 Between EGCG-treated and Non-treated Patient Groups
Time frame: 14 days
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.
Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups
Time frame: 14 days
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.
Difference of Biomarker p-Smad3 Between EGCG-treated and Non-treated Patient Groups
Time frame: 14 days
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33472968Wei 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.
- Results publication: PubMed 32160670Chapman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hal A Chapman, MD principal investigator
UC San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Epigallocatechin-3-gallate (EGCG) in people with Idiopathic Pulmonary Fibrosis, run by Hal Chapman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EGCG PK Level in Healthy Volunteers (time frame: 0, 0.5, 2, 4 hours after EGCG). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03928847, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.