Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation (PBroC)

April 16, 2019 updated by: Jackilen Shannon, Portland VA Medical Center

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.

Study Overview

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Knight Cancer Institute
      • Portland, Oregon, United States, 97239
        • Portland VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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 inhibition
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SFN-rich broccoli sprout extract capsules
Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 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
Other Names:
  • SFN
  • Sulforaphane
  • BSE
Placebo Comparator: Placebo capsules
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of Total Urine SFN (Sulforaphane) Metabolites
Time Frame: Baseline and 4-8 weeks following intervention
Collection of blood and urine specimens occurred at pre-intervention and post-intervention. Change = post-intervention level minus pre-intervention level
Baseline and 4-8 weeks following intervention
Change of Total Plasma SFN (Sulforaphane) Metabolites Level
Time Frame: Baseline and 4-8 weeks following intervention
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
Baseline and 4-8 weeks following intervention
Percentage of Ki67 Positive Cells up to 8 Weeks Post-randomization
Time Frame: Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
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.
Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
Expression of Histone Deacetylase 6 (HDAC6)
Time Frame: Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
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.
Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jackilen Shannon, PhD, Portland VA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

December 16, 2010

First Submitted That Met QC Criteria

December 22, 2010

First Posted (Estimate)

December 23, 2010

Study Record Updates

Last Update Posted (Actual)

May 1, 2019

Last Update Submitted That Met QC Criteria

April 16, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • Portland VA-09-0607
  • 2096 (PVAMC IRB)
  • 6232 (OHSU IRB)
  • 2P01CA090890-06A2 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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