Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis.
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1: healthy volunteers
- •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.
排除标准
- •co-morbidities affect hepatic function, such as HCV infection, cirrhosis, or
- •using drugs with significant hepatic toxicities
研究组 & 干预措施
EGCG PK in healthy volunteers 450 mg
Healthy volunteers: 450 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
干预措施: Epigallocatechin-3-gallate (EGCG) (Drug)
EGCG PK in healthy volunteers 600 mg
Healthy volunteers: 600 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
干预措施: Epigallocatechin-3-gallate (EGCG) (Drug)
EGCG PK in healthy volunteers 750 mg
Healthy volunteers: 750 mg Epigallocatechin-3-gallate (EGCG) capsules administered once daily by mouth
干预措施: Epigallocatechin-3-gallate (EGCG) (Drug)
EGCG treatment in ILD patients
Patients: 600 mg EGCG capsules once daily by mouth for two weeks
干预措施: Epigallocatechin-3-gallate (EGCG) (Drug)
结局指标
主要结局
Change of Serum Biomarker COMP Before and After EGCG Treatment in ILD Patients
时间窗: 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
时间窗: Day 1 to day 14
Change from baseline to day 14 in serum biomarkers associated with IPF, Periostin measured by ELISA.
EGCG PK Level in Healthy Volunteers
时间窗: 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).
Difference of Biomarker Collagen I Between EGCG-treated and Non-treated Patient Groups
时间窗: 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 Snail1 Between EGCG-treated and Non-treated Patient Groups
时间窗: 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 p-Smad3 Between EGCG-treated and Non-treated Patient Groups
时间窗: 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.
次要结局
未报告次要终点
研究者
Hal Chapman
professor
University of California, San Francisco