MedDataX Logo

Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.

NCT ID: NCT03928847

Last Updated: 2022-12-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-01

Study Completion Date

2019-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Idiopathic Pulmonary Fibrosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Open Label

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

EGCG PK in healthy volunteers 450 mg

Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Group Type OTHER

Epigallocatechin-3-gallate (EGCG)

Intervention Type DRUG

Epigallocatechin-3-gallate (EGCG) capsules

EGCG PK in healthy volunteers 600 mg

Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Group Type OTHER

Epigallocatechin-3-gallate (EGCG)

Intervention Type DRUG

Epigallocatechin-3-gallate (EGCG) capsules

EGCG PK in healthy volunteers 750 mg

Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

Group Type OTHER

Epigallocatechin-3-gallate (EGCG)

Intervention Type DRUG

Epigallocatechin-3-gallate (EGCG) capsules

No treatment control in ILD patients

Patients: not treated with EGCG

Group Type NO_INTERVENTION

No interventions assigned to this group

EGCG treatment in ILD patients

Patients: 600 mg EGCG capsules once daily by mouth for two weeks

Group Type EXPERIMENTAL

Epigallocatechin-3-gallate (EGCG)

Intervention Type DRUG

Epigallocatechin-3-gallate (EGCG) capsules

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Epigallocatechin-3-gallate (EGCG)

Epigallocatechin-3-gallate (EGCG) capsules

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Teavigo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
* using drugs with significant hepatic toxicities
Minimum Eligible Age

40 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Hal Chapman

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Hal Chapman

professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hal A Chapman, MD

Role: PRINCIPAL_INVESTIGATOR

UC San Francisco

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UC San Francisco

San Francisco, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 33472968 (View on PubMed)

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.

Reference Type RESULT
PMID: 32160670 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Consent Form for ILD Patients

View Document

Document Type: Informed Consent Form: Consent Form for Healthy Volunteers

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01HL142265

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-23008

Identifier Type: -

Identifier Source: org_study_id