Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

This study is currently recruiting participants.
Verified April 2013 by Portland VA Medical Center
Sponsor:
Collaborators:
Oregon State University
OHSU Knight Cancer Institute
Information provided by (Responsible Party):
Jackilen Shannon, Portland VA Medical Center
ClinicalTrials.gov Identifier:
NCT01265953
First received: December 16, 2010
Last updated: April 25, 2013
Last verified: April 2013

December 16, 2010
April 25, 2013
July 2011
April 2015   (final data collection date for primary outcome measure)
Identify distribution of SFN (sulforaphane) and its metabolites and HDAC (histone deacetylase) inhibition following SFN supplementation [ Time Frame: minimum 4 to maximum 8 weeks ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01265953 on ClinicalTrials.gov Archive Site
Investigate the effects (biomarkers of disease progression) of broccoli sprout supplementation on DNA methylation status and proliferation markers in a pre-biopsy setting. [ Time Frame: minimum 4 to maximum 8 weeks; prostate biopsy will be collected post-intervention when clinically-indicated ] [ Designated as safety issue: No ]
Prostate biopsy samples will be probed for 5-methyl cytosine staining by IHC; and serum and urinary DNA will undergo methyl-specific PCR for GSTp1, AR, sigma14-3-3 and P21. Cell proliferation (Ki-67 expression) and apoptosis (TUNEL expression) in SFN-supplemented and placebo prostate tissue specimens will be assessed. Collection of blood and urine specimens will occur pre-intervention and post-intervention; research only prostate biopsy specimens will be collected post-intervention at the time of the clinically-indicated prostate biopsy.
Not Provided
Not Provided
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Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation
Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

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 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).

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Prostate Cancer Prevention
  • Drug: sulforaphane glucosinolate capsules
    Four weeks sulforaphane (SFN) glucosinolate capsules: 250 mg of broccoli seed extract (30 mg sulforaphane glucosinolate), 8 capsules (4 capsules B.I.D.) daily
    Other Names:
    • sulforaphane
    • SFN
    • broccoli seed extract
  • Dietary Supplement: Gelatin capsule containing cellulose and magnesium stearate
    Four weeks placebo: 8 capsules (4 capsules B.I.D.) daily
  • Experimental: sulforaphane glucosinolate capsules
    Four weeks sulforaphane (SFN) glucosinolate capsules: 250 mg of broccoli seed extract (30 mg sulforaphane glucosinolate), 8 capsules (4 capsules B.I.D.) daily
    Intervention: Drug: sulforaphane glucosinolate capsules
  • Placebo Comparator: Placebo capsules
    Four weeks placebo capsules: 8 capsules (4 capsules B.I.D.) daily
    Intervention: Dietary Supplement: Gelatin capsule containing cellulose and magnesium stearate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
Not Provided
April 2015   (final data collection date for primary outcome measure)

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
Male
21 Years and older
Yes
Contact: Jackilen Shannon, PhD shannoja@ohsu.edu
Contact: Paige E Farris, MSW farrisp@ohsu.edu
United States
 
NCT01265953
Portland VA-09-0607, 2096, 6232, 2PO1CA090890-06A2
Yes
Jackilen Shannon, Portland VA Medical Center
Portland VA Medical Center
  • National Cancer Institute (NCI)
  • Oregon State University
  • OHSU Knight Cancer Institute
Principal Investigator: Jackilen Shannon, PhD Portland VA Medical Center
Portland VA Medical Center
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP