- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01265953
Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation (PBroC)
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
Status
Conditions
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:
- 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)
- 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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Oregon
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Portland, Oregon, United States, 97239
- OHSU Knight Cancer Institute
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Portland, Oregon, United States, 97239
- Portland VA Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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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
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Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily
Other Names:
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Placebo Comparator: Placebo capsules
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
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Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
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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
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Collection of blood and urine specimens occurred at pre-intervention and post-intervention.
Change = post-intervention level minus pre-intervention level
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Baseline and 4-8 weeks following intervention
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Change of Total Plasma SFN (Sulforaphane) Metabolites Level
Time Frame: Baseline and 4-8 weeks following intervention
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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
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Baseline and 4-8 weeks following intervention
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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
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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.
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Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
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Expression of Histone Deacetylase 6 (HDAC6)
Time Frame: Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
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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.
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Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jackilen Shannon, PhD, Portland VA Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
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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