Defined Green Tea Catechin Extract in Preventing Liver Cancer in Participants With Cirrhosis
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|ClinicalTrials.gov Identifier: NCT03278925|
Recruitment Status : Active, not recruiting
First Posted : September 12, 2017
Last Update Posted : September 30, 2022
|Condition or disease||Intervention/treatment||Phase|
|Cirrhosis||Drug: Defined Green Tea Catechin Extract Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Questionnaire Administration||Phase 1|
I. To establish maximum tolerated dose (MTD) and to collect safety data of defined green tea catechin extract (Polyphenon E/epigallocatechin gallate [EGCG]) treatment in participants with cirrhosis.
II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver.
I. To collect Polyphenon E/EGCG pharmacokinetic data in participants with cirrhosis.
II. To study the correlation between gamma-OHPdG levels and mutation frequency and deoxyribonucleic acid (DNA) damage spectrum in the p53 and beta-catenin genes in cirrhotic liver tissue.
III. To estimate the fraction of participants with liver cirrhosis that have high levels of gamma-OHPdG.
I. To assess the effects of Polyphenon E/EGCG on the grade of cirrhosis as measured by FibroScan and Fibrosis-4 (FIB-4) score.
II. To develop a liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting urinary and blood gamma-OHPdG, to correlate with liver gamma-OHPdG levels.
III. To evaluate any hepatocellular carcinoma (HCC) development during the treatment.
OUTLINE: This is a dose-escalation study.
Participants receive defined green tea catechin extract orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study intervention, participants are followed up at 28 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Single-Arm, Multicenter Pilot Study Aimed at Validating γ-OHPdG as a Biomarker and Testing the Effects of Polyphenon E on Its Levels in Patients With Cirrhosis|
|Actual Study Start Date :||August 9, 2018|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||September 30, 2022|
Experimental: Prevention (defined green tea catechin extract)
Participants receive defined green tea catechin extract PO QD or BID for 24 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Defined Green Tea Catechin Extract
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Questionnaire Administration
- Maximum tolerated dose of Polyphenon E [ Time Frame: Up to 4 weeks ]Will be defined as the dose at which =< 1 subjects out of 6 experiences a grade 3 or higher toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) criteria.
- Change in gamma-OHPdG expression in cirrhotic liver [ Time Frame: Baseline up to 24 weeks ]Will be assessed by immunohistochemistry (IHC). Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.
- Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG [ Time Frame: Up to 24 weeks ]Will use descriptive statistics.
- Change in mutation frequency in cirrhotic liver tissue [ Time Frame: Baseline up to 24 weeks ]The mutation frequencies will be correlated with the change of gamma-OHPdG level in liver tissue. Will use graphics and a nonparametric correlation measure such as Spearman's correlation.
- Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis [ Time Frame: Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1 ]Clearance of Polyphenon E will be compared among cirrhotic liver patients in this study and results from this population will be compared with non-cirrhotic historical control participants.
- Grade of cirrhosis [ Time Frame: Up to 24 weeks ]Will be assessed by FibroScan and Fibrosis-4 score.
- Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG [ Time Frame: Up to 24 weeks ]The research urine samples at screen 2 and research blood samples collected at visit 1, visit 2, and Visit 3 will be used to develop a non-invasive LC-MS and/or ELISA-based method to quantify gamma-OHPdG in urine and blood samples of collected from trial participants. Descriptive statistics (n; minimum [min]; maximum [max]; mean; median; standard deviation [SD] for continuous variables; and n, frequency for categorical variables) will be used to summarize participants demographics. Participants safety data will be tabulated according to the symptom and grade. Estimates will be presented with their 95% confidence intervals.
- Incidence of hepatocellular carcinoma [ Time Frame: At baseline and 24 weeks ]Evaluated using ultrasound/computed tomography (CT)/magnetic resonance imaging (MRI).
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): NCT03278925
|United States, District of Columbia|
|MedStar Georgetown University Hospital|
|Washington, District of Columbia, United States, 20007|
|University of Puerto Rico|
|San Juan, Puerto Rico, 00936|
|Principal Investigator:||Aiwu R He||Northwestern University|