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

December 8, 2022 updated by: Hal Chapman
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • UC San Francisco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

36 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: EGCG PK in healthy volunteers 450 mg
Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Drug: Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) capsules
Other Names:
  • Teavigo
Other: EGCG PK in healthy volunteers 600 mg
Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Drug: Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) capsules
Other Names:
  • Teavigo
Other: EGCG PK in healthy volunteers 750 mg
Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
Drug: Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) capsules
Other Names:
  • Teavigo
No Intervention: No treatment control in ILD patients
Patients: not treated with EGCG
Experimental: EGCG treatment in ILD patients
Patients: 600 mg EGCG capsules once daily by mouth for two weeks
Drug: Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) capsules
Other Names:
  • Teavigo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
0, 0.5, 2, 4 hours after EGCG
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.
Day 1 to day 14
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.
Day 1 to day 14
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.
14 days
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.
14 days
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.
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration of EGCG
Time Frame: 0, 2, 4, 12 hours post dose
The maximum plasma concentration [Cmax] following a single dose of EGCG will be determined
0, 2, 4, 12 hours post dose
Plasma exposure of EGCG
Time Frame: 0, 2, 4, 12 hours post dose
Plasma exposure measured as AUC (area under the concentration curve) following a single dose of EGCG will be determined.
0, 2, 4, 12 hours post dose
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of EGCG
Time Frame: 14 days
The incidence of treatment-emergent Adverse Events [Safety and Tolerability] following EGCG treatment will be assessed.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hal Chapman

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hal A Chapman, MD, UC San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 18, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2019

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-23008
  • R01HL142265 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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