Green Tea, Black Tea, or Water in Treating Patients With Prostate Cancer Undergoing Surgery

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00685516
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 113
• Locations: 2
• Arms: 3
• Actual Duration (Months): 91
• Patients Per Site: 56.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: Green tea contains ingredients that may prevent or slow the growth of certain cancers. It is not yet known whether green tea is more effective than black tea or water in treating prostate cancer.

PURPOSE: This randomized phase II trial is studying green tea to see how well it works compared with black tea and water in treating patients with prostate cancer undergoing surgery.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Dietary Supplement: green tea; Dietary Supplement: placebo; Dietary Supplement: decaffeinated black tea	N/A

Detailed Description

OBJECTIVES:

• to determine the effect of GT and BT consumption on apoptosis (TUNEL, ratio Bax:Bcl-2), proliferation, oxidation, and inflammation in malignant radical prostatectomy tissue compared to water control using immunohistochemistry.

• to examine levels of tea polyphenols and methylated tea polyphenol metabolites in fresh frozen radical prostatectomy tissue and urine, urinary oxidative DNA damage (8OHdG) and serum prostate-specific antigen (PSA) levels.

OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity.

• Arm II: Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity.

• Arm III: Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity.

Patients undergo radical prostatectomy.

Blood and urine samples, as well as tissue from diagnostic biopsy and radical prostatectomy specimens, are obtained for laboratory correlative studies. Samples are assessed by IHC, high-performance liquid chromatography, or mass spectrometry for changes in prostate tumor grade, stage, and margin status; concentrations of total and free tea polyphenols (i.e., EGCG, EC, EGC, ECG), theaflavins, and conjugated/colonic tea metabolites; biomarkers of prostate cancer development and progression (i.e., serum PSA, proliferation [i.e., Ki-67], apoptosis [i.e., TUNEL, Bax/Bcl-2 ratio], inflammation [i.e., NFkB]), and oxidative status (i.e., 8OhdG/dG ratio); and genotype and gene expression of metabolizing enzymes (i.e., COMT, UGT, and SULT). Serum samples are also assessed by ex vivo LNCaP cell culture assay for antiproliferative activity and by competitive chemiluminescent immunoassay for concentrations of PSA, IGF-1, IGFBP-3, testosterone, SHBG, and DHEA-sulfate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 113 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Brewed Green and Black Tea on Inflammation, Apoptosis and Oxidation in Men With Prostate Cancer
• Actual Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jan 12, 2012
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I - Green Tea Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity.	Dietary Supplement: green tea; 6 cups of green tea daily for 2-8 weeks
Placebo Comparator: Arm II - Water Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity.	Dietary Supplement: placebo; 6 cups of water daily for 2-8 weeks
Active Comparator: Arm III - Decaffeinated black tea Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity.	Dietary Supplement: decaffeinated black tea; 6 cups of decaffeinated black tea daily for 2-8 weeks

Outcome Measures

Primary Outcome Measures

1. Effect of Green Tea (GT) and Black Tea (BT) Consumption on Percentage of Cells With Positive Staining for Apoptosis, Proliferation, Oxidation, and Inflammation in Malignant Radical Prostatectomy Tissue Compared to Water Control Using Immunohistochemistry. [6 weeks]

   To determine the effect of Green Tea and Black Tea consumption on Prostate cancer tissue by examining programmed cell death, cell proliferation, cell oxidation, and cellular inflammation in that malignant radical prostatectomy tissue compared to water control using immunohistochemistry.

Secondary Outcome Measures

1. Concentration of Tea Polyphenols, Their Metabolites, and Colonic Metabolites in Prostate Tissue [6 weeks]

   Examine levels of tea polyphenols and methylated tea polyphenol metabolites in fresh frozen radical prostatectomy tissue and urine, urinary oxidative DNA damage (8OHdG) and serum prostate-specific antigen (PSA) levels.

2. Concentration of Tea Polyphenols and Methyl-metabolites in Urine After the Consumption of Green Tea (GT) and Black Tea (BT). [6 weeks]

   Concentration of tea polyphenols and methyl-metabolites in urine after the consumption of GT and BT. No polyphenols were found after water consumption

3. Prostate Specific Antigen (PSA) After the Consumption of Green Tea (GT) and Black Tea (BT). [6 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• subject consents to participate in the trial.

• subject is 40-75 years of age and has a diagnosis of adenocarcinoma of the prostate.

• Scheduled to undergo radical prostatectomy.

• The subject agrees to stop consumption of tea or tea-containing products throughout the entire intervention period except for the tea provided during study intervention.

• The subject agrees to stop consumption of dietary or vitamin supplements (e.g., lycopene, Vitamin E, selenium, genistein) or herbal supplements (e.g., saw palmetto, PC-SPES)

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 supplements

• allergy or sensitivity to multiple food items or nutritional supplements

• concurrent luteinizing hormone-releasing hormone agonists, androgen receptor blocking agents, or finasteride

• prior bilateral orchiectomy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - West Los Angeles	Los Angeles	California	United States	90073
2	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Susanne M. Henning, PhD, RD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00685516
• Other Study ID Numbers: 10-001050; R01CA116242; UCLA-061109702; CDR0000596162
• First Posted: May 28, 2008
• Last Update Posted: Dec 31, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Jonsson Comprehensive Cancer Center: adenocarcinoma of the prostate; recurrent prostate cancer; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks	Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks
Period Title: Overall Study
STARTED	42	38	33
COMPLETED	34	33	26
NOT COMPLETED	8	5	7

Baseline Characteristics

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea	Total
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks	Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks	Total of all reporting groups
Overall Participants	34	33	26	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (6.9)	61.8 (6.2)	61.4 (7.4)	61.8 (6.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	34 100%	33 100%	26 100%	93 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2.9%	0 0%	3 11.5%	4 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	5 14.7%	7 21.2%	6 23.1%	18 19.4%
White	27 79.4%	23 69.7%	13 50%	63 67.7%
More than one race	1 2.9%	3 9.1%	4 15.4%	8 8.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%	33 100%	26 100%	93 100%
Weight (KG) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	85.7 (12.2)	86.6 (14.3)	89.9 (13.4)	87.6 (14)
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	176 (21)	175 (22)	175 (22)	175.3 (22)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.2 (3.8)	27.4 (4.9)	27.4 (3.6)	27.3 (4)
Biopsy Gleason Score (percent) (participants) [Number]
6	18 52.9%	12 36.4%	11 42.3%	41 44.1%
7 (3+4)	9 26.5%	15 45.5%	9 34.6%	33 35.5%
7 (4+3)	3 8.8%	3 9.1%	3 11.5%	9 9.7%
greater than or equal to 8	4 11.8%	3 9.1%	3 11.5%	10 10.8%
Serum prostate-specific antigen (PSA) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	9.6 (5.2)	9.9 (8.5)	9.2 (4.3)	9.6 (6)

Outcome Measures

1. Primary Outcome

Title	Effect of Green Tea (GT) and Black Tea (BT) Consumption on Percentage of Cells With Positive Staining for Apoptosis, Proliferation, Oxidation, and Inflammation in Malignant Radical Prostatectomy Tissue Compared to Water Control Using Immunohistochemistry.
Description	To determine the effect of Green Tea and Black Tea consumption on Prostate cancer tissue by examining programmed cell death, cell proliferation, cell oxidation, and cellular inflammation in that malignant radical prostatectomy tissue compared to water control using immunohistochemistry.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

subjects that completed study

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity.	Placebo:patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity.	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity.
Measure Participants	34	33	26
Staining proliferation (Ki67)	2.48 (1.83)	2.3 (1.55)	4.38 (4.1)
Staining apoptosis Tunel	6.96 (8.56)	6.7 (9.1)	6.57 (8.85)
Staining oxidative DNA Damage 8OHdG	5.5 (7.4)	7.27 (10.68)	11.23 (12.01)
Staining Proliferation Bax	37.4 (11)	37.06 (8.71)	37.35 (7.58)
Staining Proliferation Bcl-2	2.92 (2.97)	5.21 (6.91)	6.48 (6.25)
NFKB cytoplasmic staining	21.23 (20.46)	22.3 (14.62)	19.21 (14.63)
NFkB nuclear staining	1.46 (1.79)	5.13 (6.37)	4.58 (6.61)

2. Secondary Outcome

Title	Concentration of Tea Polyphenols, Their Metabolites, and Colonic Metabolites in Prostate Tissue
Description	Examine levels of tea polyphenols and methylated tea polyphenol metabolites in fresh frozen radical prostatectomy tissue and urine, urinary oxidative DNA damage (8OHdG) and serum prostate-specific antigen (PSA) levels.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Concentration of tea polyphenols and methyl-metabolites in prostate tissue after the consumption of GT and BT. No polyphenols were found after water consumption. (-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) , (-)-epicatechin (EC), 4'-O-methylEGC (4'-MeEGC), 4"-O-methylEGCG (4"-OmethylEGCG).

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks	Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks
Measure Participants	34	33	26
EGCG	42.1 (32.4)	0 (0)	0 (0)
ECG	17.8 (10.1)	0 (0)	0 (0)
4" MeEGCG	38.9 (19.5)	0 (0)	0 (0)
Theaflavin	0 (0)	0 (0)	0 (0)

3. Secondary Outcome

Title	Concentration of Tea Polyphenols and Methyl-metabolites in Urine After the Consumption of Green Tea (GT) and Black Tea (BT).
Description	Concentration of tea polyphenols and methyl-metabolites in urine after the consumption of GT and BT. No polyphenols were found after water consumption
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Urine concentration of (-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) , (-)-epicatechin (EC), 4'-O-methylEGC (4'-MeEGC), 4"-O-methylEGCG (4"-OmethylEGCG).

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks	Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks
Measure Participants	34	33	26
EGC	9.2 (16)	0 (0)	.4 (.4)
EC	4.8 (6.1)	0 (0)	.3 (.3)
4'-MeEGC	8.0 (18)	0 (0)	.2 (.3)
Theaflavins	0 (0)	0 (0)	0 (0)

4. Secondary Outcome

Title	Prostate Specific Antigen (PSA) After the Consumption of Green Tea (GT) and Black Tea (BT).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Pre and post blood samples unavailable for: 4 participants in Arm I (GT group), 3 participants in Arm II (control/water group) and 3 participants in Arm III (BT group).

Arm/Group Title	Arm I - Green Tea	Arm II - Water	Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks	Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks	Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks
Measure Participants	30	30	23
Mean (Standard Deviation) [ng/mL]	8.4 (4.3)	10.0 (9.0)	9.6 (6.0)

Adverse Events

Time Frame	Up to 8 weeks
Arm/Group Title	Arm I - Green Tea		Arm II - Water		Arm III - Decaffeinated Black Tea
Arm/Group Description	Patients receive 6 cups of green tea daily for 2-8 weeks in the absence of unacceptable toxicity. green tea: 6 cups of green tea daily for 2-8 weeks		Patients receive 6 cups of water daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: 6 cups of water daily for 2-8 weeks		Patients receive 6 cups of decaffeinated black tea daily for 2-8 weeks in the absence of unacceptable toxicity. decaffeinated black tea: 6 cups of decaffeinated black tea daily for 2-8 weeks
All Cause Mortality
	Arm I - Green Tea		Arm II - Water		Arm III - Decaffeinated Black Tea
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)		0/26 (0%)
Serious Adverse Events
	Arm I - Green Tea		Arm II - Water		Arm III - Decaffeinated Black Tea
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Arm I - Green Tea		Arm II - Water		Arm III - Decaffeinated Black Tea
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.