Clinical trial NCT01912820: Effect of Quercetin on Green Tea Polyphenol Uptake in Prostate Tissue From Patients With Prostate Cancer Undergoing Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-07-31
Enrollment: 32
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Green tea polyphenols, quercetin and their metabolite concentration in blood and prostate tissue
timeFrame: On the day of surgery
Secondary outcomes:
measure: Protein and gene expression of COMT in prostate tissue
timeFrame: Day of surgery
measure: Protein and gene expression of DNMT1 in prostate tissue
timeFrame: Day of surgery
measure: Protein and gene expression of MRP1 in prostate tissue
timeFrame: Day of surgery
measure: COMT activity in red blood cells
timeFrame: Week 3
measure: Genotype of COMT (high [H]/H, low [L]/L or H/L)
timeFrame: Week 3
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Veterans Administration Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Susanne Henning, MD
role: PRINCIPAL_INVESTIGATOR
References: