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

Early Phase 1CompletedNCT03928847

Hal Chapman35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Epigallocatechin-3-gallate (EGCG)DRUG

Epigallocatechin-3-gallate (EGCG) capsules

Eligibility

Sex: ALLMin age: 40 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

UC San Francisco

San Francisco, California, United States

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 14 days

Data from ClinicalTrials.gov

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