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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03928847
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : January 13, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of California, San Francisco

Study Description
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Brief 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. 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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Epigallocatechin-3-gallate (EGCG) Early Phase 1

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Other
Official Title: Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

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Arms and Interventions
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Arm Intervention/treatment
Experimental: EGCG treatment

Healthy volunteers: 450 mg, 600 mg, or 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth

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

 Drug: Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) capsules
Other Name: Teavigo


Outcome Measures
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Primary Outcome Measures :
  1. Analysis of biomarker levels from Lung tissue specimens [ Time Frame: Day 14 ]
    LOXL2 activity and TGFbeta1 signaling biomarkers such as Snail1 and pSmad3 will be measured in lung tissue from subjects treated with EGCG and compared levels seen in to lung tissue from untreated control subjects.

  2. Change from baseline in urinary biomarkers of LOXL2 collagen crosslinking [ Time Frame: Change from day 1 to day 14 ]
    Change from baseline to day 14 in biomarkers representative of LOXL2 collagen crosslinking will be measured in urine samples collected on day 1 and day 14.

  3. Analysis of serum biomarker Periostin and COMP levels from blood specimens [ Time Frame: Change from day 1 to day 14 ]
    Change from baseline to day 14 in serum biomarkers associated with IPF


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.


Eligibility Criteria
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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928847


Contacts
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Contact: Hal A Chapman, MD 415-514-1210 Hal.Chapman@ucsf.edu

Locations
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United States, California
UC San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Hal A Chapman, MD    415-514-1210      
Sponsors and Collaborators
University of California, San Francisco
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Hal A Chapman, MD UC San Francisco
More Information
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Publications of Results:

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03928847    
Other Study ID Numbers: 17-23008
R01HL142265 ( U.S. NIH Grant/Contract )
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Epigallocatechin gallate
 Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents