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Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

21 Years
Open (Enrolling)
Prostate Cancer Prevention

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Trial Information

Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

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 SFN
supplementation in subjects at risk for prostate cancer (Primary Endpoints)

2. Investigate the effects of broccoli sprout supplementation on DNA methylation status
and proliferation markers in a pre-biopsy setting (secondary analysis)

The effects of short-term SFN supplementation 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 four-week supply of either SFN
glucosinolate capsules or matching placebo, as dispensed by the Research Pharmacy.

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).

Inclusion Criteria:

- Men scheduled for a prostate biopsy

- Age 21 years or older

- Signed informed subject consent

Exclusion Criteria:

- Definitive diagnosis with prostate cancer

- Significant active medical illness which in the opinion of the investigator or
clinician would preclude protocol treatment

- Diagnosis of liver disease as noted on the patient problem list or baseline total
bilirubin greater than institutional upper limit of normal

- Subject reported allergy or sensitivity to cruciferous vegetables

- Use of oral antibiotics, with the exception of doxycycline, within three months prior
to randomization

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

- Current oral steroid therapy

- Current therapy with valproate or other pharmacological drugs associated with HDAC

- Diagnosed dementia as noted on the patient problem list or other significant mental
illness that may impact the subjects' ability to follow instructions or comply with
the study protocol

- Patient may not be a part of another flagged study

- Patients already taking SFN dietary supplements

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Outcome Measure:

Identify distribution of SFN (sulforaphane) and its metabolites and HDAC (histone deacetylase) inhibition following SFN supplementation

Outcome Description:

In subjects at risk for prostate cancer by examining expression of acetylated H3 and H4, and absolute histone levels in peripheral blood and in prostate tissue. Presence of SFN and its metabolites (SFN-Cys, SFN-NAC) will be analyzed in plasma, urine and prostate tissue. Collection of blood and urine specimens will occur at pre-intervention and post-intervention; research only prostate biopsy specimens will be collected post-intervention at the time of the clinically-indicated prostate biopsy.

Outcome Time Frame:

minimum 4 to maximum 8 weeks

Safety Issue:


Principal Investigator

Jackilen Shannon, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Portland VA Medical Center


United States: Food and Drug Administration

Study ID:

Portland VA-09-0607



Start Date:

July 2011

Completion Date:

Related Keywords:

  • Prostate Cancer Prevention
  • cancer prevention
  • isothiocyanate
  • sulforaphane
  • Prostatic Neoplasms



OHSU Knight Cancer Institute Portland, Oregon  97239
Portland VA Medical Center Portland, Oregon  97239