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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 32
- Locations
- 2
- Primary Endpoint
- Green tea polyphenols, quercetin and their metabolite concentration in blood and prostate tissue
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 40 Years to 75 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Arm I (quercetin, green tea extract)
Patients receive GT extract PO BID and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: quercetin (Drug)
Arm I (quercetin, green tea extract)
Patients receive GT extract PO BID and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: green tea extract (Dietary Supplement)
Arm I (quercetin, green tea extract)
Patients receive GT extract PO BID and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: therapeutic conventional surgery (Procedure)
Arm I (quercetin, green tea extract)
Patients receive GT extract PO BID and quercetin PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: laboratory biomarker analysis (Other)
Arm II (GT extract, placebo)
Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: green tea extract (Dietary Supplement)
Arm II (GT extract, placebo)
Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: placebo (Other)
Arm II (GT extract, placebo)
Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: therapeutic conventional surgery (Procedure)
Arm II (GT extract, placebo)
Patients receive GT extract PO BID and placebo PO BID for 3-6 weeks before undergoing prostatectomy.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Green tea polyphenols, quercetin and their metabolite concentration in blood and prostate tissue
Time Frame: On the day of surgery
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.
Secondary Outcomes
- Protein and gene expression of MRP1 in prostate tissue(Day of surgery)
- Protein and gene expression of COMT in prostate tissue(Day of surgery)
- Protein and gene expression of DNMT1 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)(Week 3)