Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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All Drugs and Chemicals

Other Dietary Supplements

Sulforaphane

Phenethyl isothiocyanate

Protective Agents

Phenethylisothiocyanate

Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily

Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily

Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily

SFN-rich broccoli sprout extract capsules

Gelatin capsule containing microcrystalline cellulose.

Jackilen Shannon, PhD

The objective of the study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene expression via epigenetic modifications (changes in gene expression) and may prevent prostate cancer development.

The investigators have found that sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, inhibits histone deacetylase (HDAC) activity in human colorectal and prostate cancer cells.

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. The precise etiologic factors that initiate and enhance the progression of prostate cancer remain unknown, but epigenetic alterations and diet/lifestyle factors have come forth as significant contributing factors. Epidemiologic studies suggest that cruciferous vegetable intake decreases the risk for prostate cancer. The long-term goal of this proposal is to identify mechanisms by which dietary compounds, such as those found in cruciferous vegetables decrease prostate cancer risk. The objective of the study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene expression via epigenetic modifications and may prevent prostate cancer development.

The investigators have found that SFN, an isothiocyanate found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells.

Targeting the epigenome, including the use of HDAC and DNA methyltransferase (DNMT) inhibitors, is an evolving strategy for cancer chemoprevention and both have shown promise in cancer clinical trials.

This Randomized, Double Blind, Clinical Trial will address the following objectives:

1. Identify distribution of SFN and its metabolites and HDAC inhibition following supplementation with an SFN-rich broccoli sprout extract in subjects at risk for prostate cancer (Primary Endpoints)
2. Investigate the effects of supplementation with an SFN-rich broccoli sprout extract on DNA methylation status and proliferation markers in a pre-biopsy setting (secondary analysis)

The effects of short-term supplementation with an SFN-rich broccoli sprout extract on benign epithelial tissue will be studied in men characterized as being at risk for prostate cancer in a randomized, placebo-controlled trial. Men scheduled for prostate biopsy will be recruited into the trial.

Following successful completion of the consent, two 10 mL blood specimens for study analyses, a 4 mL specimen for total bilirubin assessment will be drawn and the subject will provide a urine sample. The study coordinator will explain the Diet History questionnaires (DHQ) and administer the risk factor and adverse event (AE) questionnaires in order to obtain data on potential confounding dietary variables and gain subjects' baseline symptoms.

The study coordinator will provide the subject with a month' supply of either an SFN-rich broccoli sprout extract (BSE) capsule which consist of 200µmol of sulforaphane (SFN) or matching placebo, as dispensed by the Research Pharmacy. The matching placebo for the BSE consists of a gelatin capsule containing microcrystalline cellulose.

Around every 2 weeks, study coordinator will call to complete AE reporting and any changes in medications or supplements and complete brief cruciferous vegetable intake checklist. Subjects will return any unused study "drug" to the study coordinator at the time of biopsy (or at the 4 week visit if subject's prostate biopsy is delayed).

Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

Collection of blood and urine specimens occurred at pre-intervention and post-intervention. Change = post-intervention level minus pre-intervention level

In subjects at risk for prostate cancer, presence of SFN was analyzed in plasma. Collection of blood specimens occurred at pre-intervention and post-intervention. The Change = post-intervention level minus pre-intervention level

Ki67 is a biomarker of disease progression. Immunohistochemical (IHC) analysis of Ki67 was performed using research only prostate biopsy specimens collected post-intervention at the time of the clinically-indicated prostate biopsy.

Immunohistochemical (IHC) analysis of HDAC6 expression using research-only prostate biopsy tissue collected post-intervention at the time of the clinically-indicated prostate biopsy. A modified Histo-score (H-score) was calculated, which involved semiquantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate, and 3 strong) and percentage of positive cells. H-score ranged from 0 to 300 with 300 the strongest expression.

National Cancer Institute (NCI)

Oregon State University

OHSU Knight Cancer Institute

Portland VA Medical Center

Staff Scientist

Subjects in this group were administered with broccoli sprout extract.

Supplement

Subjects in this group were administered with placebo.

Placebo

Four weeks broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily

Broccoli Sprout Extract Capsules

Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily

Dietary Supplement: Gelatin capsule containing microcrystalline cellulose

Placebo Capsules

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr.Jackilen Shannon

Not all subjects had urine samples for analysis, therefore, the total number of subjects in this urine analysis is different from total number of enrolled subjects.

Change of Total Urine SFN (Sulforaphane) Metabolites

We missed blood samples from some subjects, therefore, total number of subjects analyzed for the plasma-based analysis is different from the number of total enrolled subjects.

Change of Total Plasma SFN (Sulforaphane) Metabolites Level

Some subjects did not have post-intervention prostate tissue that can be used for IHC analysis, therefore, the overall number of participants analyzed for IHC analysis is different from the total enrolled subjects.

Spots Global Cancer Trial Database for gelatin capsule containing microcrystalline cellulose.