Fish Oil and Green Tea Extract in Preventing Prostate Cancer in Patients Who Are at Risk for Developing Prostate Cancer

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00253643
• Collaborator: United States Department of Defense (U.S. Fed), National Cancer Institute (NCI) (NIH)
• Enrollment: 89
• Locations: 3
• Arms: 4
• Duration (Months): 101
• Patients Per Site: 29.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of fish oil and/or green tea may prevent prostate cancer.

PURPOSE: This randomized clinical trial is studying how well a fish oil and/or green tea supplement works in preventing prostate cancer in patients with prostatic intraepithelial neoplasia or who are at risk for developing prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Precancerous Condition; Prostate Cancer	Dietary Supplement: green tea catechin extract; Dietary Supplement: fish oil; Other: placebo; Other: placebo	N/A

Detailed Description

OBJECTIVES:

• Determine the cancer preventing effects of fish oil supplementation and green tea extract use on markers of alteration in lipid metabolism in prostate tissue samples.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to age (under 65 vs 65 and over). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral fish oil three times daily and oral green tea extract twice daily.

• Arm II: Patients receive an oil placebo three times daily and oral green tea extract twice daily.

• Arm III: Patients receive oral fish oil three times daily and a placebo twice daily.

• Arm IV: Patients receive an oil placebo three times daily and another placebo twice daily.

Treatment in one of the above-listed arms continues for up to 20 weeks in the absence of disease progression or unacceptable toxicity.

All patients undergo a prostate biopsy on the last day of study treatment.

After completion of study treatment, patients receive a follow-up phone call at/around 30 days later.

PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Catechins and Omega-3 Fatty Acids Impact on Fatty Acid Synthase Activity in the Prostate: A Randomized Controlled Trial
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (FO, GT catechin extract) Patients receive oral fish oil (FO) 3/day and oral green tea (GT) extract 2/day	Dietary Supplement: green tea catechin extract; Given orally 2 times/day; Other Names: Polyphenon E ; Dietary Supplement: fish oil; Given orally 3 times/day; Other Names: omega-3 fatty acid, n-3 fatty acid, omega-3 polyunsaturated fatty acid, omega-3 PUFA
Experimental: ArmII (FO placebo, GT catechin extract) Patients receive a fish oil (FO) placebo 3/day and oral green tea (GT) extract 2/day	Dietary Supplement: green tea catechin extract; Given orally 2 times/day; Other Names: Polyphenon E ; Other: placebo; Given green tea placebo orally 2 times/day; Other Names: PLCB
Experimental: Arm III (FO, GT placebo) Patients receive oral fish oil (FO) 3/day and a placebo mimicking green tea (GT) catechins 2/day	Dietary Supplement: fish oil; Given orally 3 times/day; Other Names: omega-3 fatty acid, n-3 fatty acid, omega-3 polyunsaturated fatty acid, omega-3 PUFA ; Other: placebo; Given olive oil placebo orally 3 times/day; Other Names: PLCB, olive oil
Placebo Comparator: Arm IV (FO placebo, GT placebo) Patients receive a fish oil (FO) placebo mimicking fish oil 3/day and another placebo mimicking green tea (GT) catechins 2/day	Other: placebo; Given olive oil placebo orally 3 times/day; Other Names: PLCB, olive oil ; Other: placebo; Given green tea placebo orally 2 times/day; Other Names: PLCB

Outcome Measures

Primary Outcome Measures

1. Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) [Baseline (pre-intervention) and end of study (time to surgery for those with malignant findings or up to 8 weeks for those with benign biopsies, post-intervention)]

   Sections of paraffin-embedded prostate biopsy tissue were stained for fatty acid synthase (FAS) expression. The FAS Summary Score was calculated as the product of percent stained (1=0-25%, 2=25-50%, 3=51-75%, 4=76-100%) and stain intensity (0-3) by immunohistochemistry. The range of the product is 0-300.

2. Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention [End of study]

   Cell Proliferation by Ki67 is calculated as the percent stained by immunohistochemistry. Ki-67 values were log-transformed because the original distribution was skewed. Analysis was done on log-base2 transformed values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

INCLUSION CRITERIA:

• Clinician recommends repeat biopsy of the prostate ("Repeat" is defined as any recommended biopsy of the prostate subsequent to an earlier biopsy of the prostate)

EXCLUSION CRITERIA:

• Definitive invasive prostate cancer on initial biopsy

• Significant active medical illness that in the opinion of the clinician would preclude protocol treatment.

• History of ventricular tachycardia or ventricular fibrillation

• Subject reported use of fish oil (greater than 1 gram per day) or green tea supplement within 30 days before Day 1 of study treatment

• Subject reported use of fish oil ≤ 1 gram per day and unwilling to discontinue use for the duration of the trial

• Use of warfarin or need for therapeutic anticoagulation at time of biopsy or at anytime during the course of the trial.

• Subject reported allergy or sensitivity to fish oil, olive oil or green tea

• Subject reported history of hemophilia, van Willebrands disease or other bleeding disorder, except when the subject is evaluated by a hematologist who determines that fish oil supplementation is not contraindicated.

• Total bilirubin greater than institutional upper limit of normal

• Concurrent high risk study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Center for Health Research	Portland	Oregon	United States	97227
2	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239-3098
3	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97239

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• United States Department of Defense
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jackilen Shannon, PhD, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jackie Shannon, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00253643
• Other Study ID Numbers: CDR0000443617; P30CA069533; OHSU-CI-CPC-04131-LX; VAMC-04-0303/ M1016; DOD-W81XWH-04-1-0296; OHSU-1117; KPNW-NW-05SLIEB-01
• First Posted: Nov 15, 2005
• Last Update Posted: Apr 18, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Jackie Shannon, Principal Investigator, OHSU Knight Cancer Institute: prostate cancer; precancerous condition
• Additional relevant MeSH terms: Prostatic Neoplasms; Precancerous Conditions; Epigallocatechin gallate

Study Results

Participant Flow

Arm/Group Title	Arm I (Fish Oil, Green Tea Catechin Extract)	Arm II (Fish Oil Placebo, Green Tea Catechin Extract)	Arm III (Fish Oil, Green Tea Placebo)	Arm IV (Fish Oil Placebo, Green Tea Placebo)
Arm/Group Description	Patients receive oral fish oil 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day fish oil: Given orally 3 times/day laboratory biomarker analysis: Correlative studies questionnaire administration: Ancillary studies	Patients receive an oil placebo 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day placebo: Given olive oil placebo orally 3 times/day laboratory biomarker analysis: Correlative studies questionnaire administration: Ancillary studies	Patients receive oral fish oil 3/day and a placebo mimicking green tea catechins 2/day fish oil: Given orally 3 times/day placebo: Given green tea placebo orally 2 times/day laboratory biomarker analysis: Correlative studies questionnaire administration: Ancillary studies	Patients receive an oil placebo mimicking fish oil 3/day and another placebo mimicking green tea catechins 2/day placebo: Given olive oil placebo orally 3 times/day placebo: Given green tea placebo orally 2 times/day laboratory biomarker analysis: Correlative studies questionnaire administration: Ancillary studies
Period Title: Overall Study
STARTED	14	15	29	31
COMPLETED	14	15	28	28
NOT COMPLETED	0	0	1	3

Baseline Characteristics

Arm/Group Title	Arm I (Fish Oil, Green Tea Catechin Extract)	Arm II (Fish Oil Placebo, Green Tea Catechin Extract)	Arm III (Fish Oil, Green Tea Placebo)	Arm IV (Fish Oil Placebo, Green Tea Placebo)	Total
Arm/Group Description	Patients receive oral fish oil 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day fish oil: Given orally 3 times/day	Patients receive an oil placebo 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day placebo: Given olive oil placebo orally 3 times/day	Patients receive oral fish oil 3/day and a placebo mimicking green tea catechins 2/day fish oil: Given orally 3 times/day placebo: Given green tea placebo orally 2 times/day	Patients receive an oil placebo mimicking fish oil 3/day and another placebo mimicking green tea catechins 2/day placebo: Given olive oil placebo orally 3 times/day placebo: Given green tea placebo orally 2 times/day	Total of all reporting groups
Overall Participants	14	15	28	28	85
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 57.1%	10 66.7%	18 64.3%	19 67.9%	55 64.7%
>=65 years	6 42.9%	5 33.3%	10 35.7%	9 32.1%	30 35.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	14 100%	15 100%	28 100%	28 100%	85 100%
Region of Enrollment (participants) [Number]
United States	14 100%	15 100%	28 100%	28 100%	85 100%
Diagnosis (participants) [Number]
Benign	9 64.3%	11 73.3%	16 57.1%	21 75%	57 67.1%
Prostate Cancer	2 14.3%	1 6.7%	6 21.4%	6 21.4%	15 17.6%
Prostatic Intraepithelial Neoplasia (PIN)	3 21.4%	3 20%	6 21.4%	1 3.6%	13 15.3%

Outcome Measures

1. Primary Outcome

Title	Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score)
Description	Sections of paraffin-embedded prostate biopsy tissue were stained for fatty acid synthase (FAS) expression. The FAS Summary Score was calculated as the product of percent stained (1=0-25%, 2=25-50%, 3=51-75%, 4=76-100%) and stain intensity (0-3) by immunohistochemistry. The range of the product is 0-300.
Time Frame	Baseline (pre-intervention) and end of study (time to surgery for those with malignant findings or up to 8 weeks for those with benign biopsies, post-intervention)

Outcome Measure Data

Analysis Population Description

Number of participants for recruitment was based on power calculations. All participants consented and randomized were included in analyses. Analysis was intention to treat. No imputations for missing data were conducted.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group Description	Fish oil, Green Tea catechin extract	Fish oil placebo, Green Tea catechin extract	Fish oil, Green Tea placebo	Fish oil placebo, Green Tea placebo
Measure Participants	14	15	28	28
PRE data	147 (98.6)	158.8 (84.6)	138.3 (63.8)	102.3 (85.9)
POST data	140.7 (100.3)	159.3 (75.5)	145.2 (72.2)	152.2 (80.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Mixed effects model to assess the effect time (pre vs. post) and treatment (GTFO, GT, FO and Placebo) on FAS summary scores
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1521
	Comments	Utilized a priori threshold for statistical significance of 0.05.
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention
Description	Cell Proliferation by Ki67 is calculated as the percent stained by immunohistochemistry. Ki-67 values were log-transformed because the original distribution was skewed. Analysis was done on log-base2 transformed values.
Time Frame	End of study

Outcome Measure Data

Analysis Population Description

Number of participants for recruitment was based on power calculations. All participants consented and randomized were included in analyses. Analysis was intention to treat. No imputations for missing data were conducted.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group Description	Fish oil, Green Tea catechin extract	Fish oil placebo, Green Tea catechin extract	Fish oil, Green Tea placebo	Fish oil placebo, Green Tea placebo
Measure Participants	14	15	28	28
Median (Full Range) [%age of cells & nuclei stained]	18.5	8	10	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Mixed effects model to assess the effect of time (pre vs. post) and treatment (GTFO, GT, FO and Placebo) on Ki-67
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1573
	Comments	A priori threshold for statistical significance is 0.05.
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Adverse event data were collected every month the subject was on study via questionnaire over the phone. We conducted a 30-day follow-up phone call and utilized our adverse event questionnaire to capture this information at baseline as well.
Arm/Group Title	Arm I (Fish Oil, Green Tea Catechin Extract)		Arm II (Fish Oil Placebo, Green Tea Catechin Extract)		Arm III (Fish Oil, Green Tea Placebo)		Arm IV (Fish Oil Placebo, Green Tea Placebo)
Arm/Group Description	Patients receive oral fish oil 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day fish oil: Given orally 3 times/day		Patients receive an oil placebo 3/day and oral green tea extract 2/day green tea catechin extract: Given orally 2 times/day placebo: Given olive oil placebo orally 3 times/day		Patients receive oral fish oil 3/day and a placebo mimicking green tea catechins 2/day fish oil: Given orally 3 times/day placebo: Given green tea placebo orally 2 times/day		Patients receive an oil placebo mimicking fish oil 3/day and another placebo mimicking green tea catechins 2/day placebo: Given olive oil placebo orally 3 times/day placebo: Given green tea placebo orally 2 times/day
All Cause Mortality
	Arm I (Fish Oil, Green Tea Catechin Extract)		Arm II (Fish Oil Placebo, Green Tea Catechin Extract)		Arm III (Fish Oil, Green Tea Placebo)		Arm IV (Fish Oil Placebo, Green Tea Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Fish Oil, Green Tea Catechin Extract)		Arm II (Fish Oil Placebo, Green Tea Catechin Extract)		Arm III (Fish Oil, Green Tea Placebo)		Arm IV (Fish Oil Placebo, Green Tea Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/15 (0%)		0/29 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Fish Oil, Green Tea Catechin Extract)		Arm II (Fish Oil Placebo, Green Tea Catechin Extract)		Arm III (Fish Oil, Green Tea Placebo)		Arm IV (Fish Oil Placebo, Green Tea Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		2/15 (13.3%)		5/29 (17.2%)		1/31 (3.2%)
Gastrointestinal disorders
Bloating (grade 2)	0/14 (0%)		0/15 (0%)		0/29 (0%)		1/31 (3.2%)
Gas/Flatulence (grade 2)	0/14 (0%)		1/15 (6.7%)		1/29 (3.4%)		0/31 (0%)
Burping (grade 2)	0/14 (0%)		1/15 (6.7%)		0/29 (0%)		1/31 (3.2%)
Nausea/Vomiting (grade 2)	0/14 (0%)		1/15 (6.7%)		1/29 (3.4%)		0/31 (0%)
Upset Stomach (grade 2)	0/14 (0%)		0/15 (0%)		1/29 (3.4%)		1/31 (3.2%)
Diarrhea/ Loose Stool (grade 2)	0/14 (0%)		0/15 (0%)		1/29 (3.4%)		0/31 (0%)
Heartburn (grade 2)	0/14 (0%)		0/15 (0%)		0/29 (0%)		1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Muscle Pain (grade 2)	1/14 (7.1%)		1/15 (6.7%)		0/29 (0%)		1/31 (3.2%)
Nervous system disorders
Headache (grade 2)	0/14 (0%)		0/15 (0%)		2/29 (6.9%)		1/31 (3.2%)
Skin and subcutaneous tissue disorders
Bruising (grade 2)	0/14 (0%)		1/15 (6.7%)		1/29 (3.4%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.