Effect of Quercetin on Green Tea Polyphenol Uptake in Prostate Tissue From Patients With Prostate Cancer Undergoing Surgery

A Phase I Randomized, Double-Blind, Placebo-Controlled Two-Arm Study of Quercetin and Green Tea to Enhance the Bioavailability of Green Tea Polyphenols in Men Scheduled for Prostatectomy

This randomized pilot phase I trial will evaluate if quercetin enhances the uptake of green tea polyphenols in the prostate tissue of men taking green tea extract and undergoing radical prostatectomy. Side effects of green tea extract and quercetin in combination with green tea extract will also be evaluated. In preclinical studies, green tea polyphenols have anticancer and cancer preventative effects in a number of malignancies. Likewise, in preclinical studies quercetin was found to enhance the anticancer effects of green tea. This trial is designed to translate these findings forward in a short-term human intervention trial.

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage III Prostate Cancer; Adenocarcinoma of the Prostate; Stage IV Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: placebo; Procedure: therapeutic conventional surgery; Dietary supplement: green tea extract; Drug: quercetin

Detailed Description

PRIMARY OBJECTIVES:

I. To investigate the prostate tissue concentration of epigallocatechin gallate (EGCG), epicatechin gallate (ECG) and quercetin and their methylated metabolites in men scheduled for prostatectomy and consuming green tea (GT)extract (N=15) or GTextract with quercetin (N=15) for 3 weeks prior to prostatectomy.

II. To determine the concentration of EGCG, ECG, epigallocatechin (EGC), epicatechin (EC) and quercetin and the methylated metabolites in plasma collected before (T=0) and two hours (T=2) after the intake of the morning dose of GTextract and placebo or GTextract with quercetin during the third week of intervention.

III. To determine the effect of GTextract/quercetin intervention on reducing the enzyme activity and protein and gene expression of catechol-O-methyltransferase (COMT) and deoxyribonucleic (DNA) (cytosine-5) methyltransferase 1 (DNMT1) as well as protein and gene expression of multidrug resistance transport protein 1 (MRP1) in prostate tissue collected in specific aim 1 and COMT activity in erythrocytes from blood collected at baseline and week 3.

IV. To determine the inter-individual variation in genotype of COMT in buffy coat DNA.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive GT extract orally (PO) twice daily (BID) and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.

ARM II: Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center
    • Los Angeles, California, United States, 90073
      • Veterans Administration Los Angeles Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subjects consent to participate in the trial
• The subject has a diagnosis of adenocarcinoma of the prostate
• The subject is scheduled to undergo radical prostatectomy
• The subject agrees to stop consuming tea or tea-containing products and quercetin supplements throughout the entire intervention period except for the green tea extract and quercetin provided during study intervention

Exclusion Criteria:

• History of hepatitis or liver dysfunction
• Ongoing alcohol abuse
• Significant medical or psychiatric conditions that would make the patient a poor protocol candidate
• Prior sensitivity or allergic reaction to tea, tea products or tea and quercetin supplements
• Allergies to multiple food items or nutritional supplements
• Taking luteinizing hormone-releasing hormone (LHRH) agonists, androgen receptor blocking agents, finasteride, or has undergone bilateral orchiectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (quercetin, green tea extract); Patients receive GT extract PO BID and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.	Other: laboratory biomarker analysis; Correlative studies; Procedure: therapeutic conventional surgery; Undergo prostatectomy; Dietary supplement: green tea extract; Given PO; Other Names: green tea polyphenols; Drug: quercetin; Given PO; Other Names: C.I. natural yellow 10
Placebo Comparator: Arm II (GT extract, placebo); Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.	Other: laboratory biomarker analysis; Correlative studies; Other: placebo; Given PO; Other Names: PLCB; Procedure: therapeutic conventional surgery; Undergo prostatectomy; Dietary supplement: green tea extract; Given PO; Other Names: green tea polyphenols

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Green tea polyphenols, quercetin and their metabolite concentration in blood and prostate tissue	Means and standard deviation will be calculated and the statistical difference between treatment with GTextract + quercetin compared to GTextract + placebo will be determined using Student's t-test computed by one-way analysis of variance models.	On the day of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein and gene expression of COMT in prostate tissue		Day of surgery
Protein and gene expression of DNMT1 in prostate tissue		Day of surgery
Protein and gene expression of MRP1 in prostate tissue		Day of surgery
COMT activity in red blood cells		Week 3
Genotype of COMT (high [H]/H, low [L]/L or H/L)	Gene-association analyses will be conducted for COMT polymorphic variants within each intervention group using SAS Genetics, version 9.1	Week 3

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Susanne Henning, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): January 31, 2016
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Quercetin
• Other Study ID Numbers: 12-000886; NCI-2013-01153 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R03CA171583 (U.S. NIH Grant/Contract)