This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
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: June 16, 2017
Last verified: June 2017
  Purpose

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.


Condition Intervention
Prostate Cancer Prevention Drug: sulforaphane glucosinolate capsules Dietary Supplement: Gelatin capsule containing cellulose and magnesium stearate

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

Resource links provided by NLM:


Further study details as provided by Jackilen Shannon, Portland VA Medical Center:

Primary Outcome Measures:
  • Change of Total Urine SFN (Sulforaphane) Metabolites [ Time Frame: minimum 4 to maximum 8 weeks ]
    Collection of blood and urine specimens occurred at pre-intervention and post-intervention. Change = post-intervention level minus pre-intervention level

  • Change of Total Plasma SFN (Sulforaphane) Metabolites Level [ Time Frame: minimum 4 to maximum 8 weeks ]
    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

  • Expression of Ki67 [ Time Frame: minimum 4 to maximum 8 weeks; 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.

  • Expression of Histone Deacetylase 6 (HDAC6) [ Time Frame: minimum 4 to maximum 8 weeks; 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.


Enrollment: 98
Study Start Date: July 2011
Study Completion Date: December 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Placebo Comparator: Placebo capsules
Four weeks placebo capsules: 8 capsules (4 capsules B.I.D.) daily
Dietary Supplement: Gelatin capsule containing cellulose and magnesium stearate
Four weeks placebo: 8 capsules (4 capsules B.I.D.) daily

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 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).

  Eligibility

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265953

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Portland VA Medical Center
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Portland VA Medical Center
National Cancer Institute (NCI)
Oregon State University
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Jackilen Shannon, PhD Portland VA Medical Center
  More Information

Responsible Party: Jackilen Shannon, Staff Scientist, Portland VA Medical Center
ClinicalTrials.gov Identifier: NCT01265953     History of Changes
Other Study ID Numbers: Portland VA-09-0607
2096 ( Other Identifier: PVAMC IRB )
6232 ( Other Identifier: OHSU IRB )
2P01CA090890-06A2 ( U.S. NIH Grant/Contract )
Study First Received: December 16, 2010
Results First Received: May 12, 2017
Last Updated: June 16, 2017

Keywords provided by Jackilen Shannon, Portland VA Medical Center:
cancer prevention
isothiocyanate
sulforaphane

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Sulforafan
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 19, 2017