Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2096 | Other Identifier | PVAMC IRB | |
| 6232 | Other Identifier | OHSU IRB | |
| 2P01CA090890-06A2 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Oregon State University | OTHER |
| OHSU Knight Cancer Institute | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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:
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SFN-rich broccoli sprout extract capsules | Experimental | Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily |
|
| Placebo capsules | Placebo Comparator | Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SFN-rich broccoli sprout extract capsules | Drug | Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of Total Urine SFN (Sulforaphane) Metabolites | 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 | 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 | 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) | 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 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jackilen Shannon, PhD | Portland VA Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| OHSU Knight Cancer Institute | Portland | Oregon | 97239 | United States | ||
| Portland VA Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31155953 | Derived | Zhang Z, Garzotto M, Davis EW 2nd, Mori M, Stoller WA, Farris PE, Wong CP, Beaver LM, Thomas GV, Williams DE, Dashwood RH, Hendrix DA, Ho E, Shannon J. Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial. Nutr Cancer. 2020;72(1):74-87. doi: 10.1080/01635581.2019.1619783. Epub 2019 Jun 1. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Supplement | Subjects in this group were administered with broccoli sprout extract. |
| FG001 | Placebo | Subjects in this group were administered with placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Broccoli Sprout Extract Capsules | Four weeks broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily |
| BG001 | Placebo Capsules |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of Total Urine SFN (Sulforaphane) Metabolites | Collection of blood and urine specimens occurred at pre-intervention and post-intervention. Change = post-intervention level minus pre-intervention level | Not all subjects had urine samples for analysis, therefore, the total number of subjects in this urine analysis is different from total number of enrolled subjects. | Posted | Mean | Standard Error | micromolar (µM) concentrations of urina | Baseline and 4-8 weeks following intervention |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Supplement | Subjects in this group were administered with broccoli sprout extract. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr.Jackilen Shannon | Oregon Health & Science University | 503-418-9860 | shannoja@ohsu.edu |
Not provided
| ID | Term |
|---|---|
| C016766 | sulforaphane |
| D005780 | Gelatin |
| ID | Term |
|---|---|
| D012596 | Scleroproteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Gelatin capsule containing microcrystalline cellulose. | Dietary Supplement | Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily |
|
| Portland |
| Oregon |
| 97239 |
| United States |
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
Dietary Supplement: Gelatin capsule containing microcrystalline cellulose
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
|
|
| Primary | Change of Total Plasma SFN (Sulforaphane) Metabolites Level | 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 | We missed blood samples from some subjects, therefore, total number of subjects analyzed for the plasma-based analysis is different from the number of total enrolled subjects. | Posted | Mean | Standard Error | micromolar (µM) | Baseline and 4-8 weeks following intervention |
|
|
|
| Primary | Percentage of Ki67 Positive Cells up to 8 Weeks Post-randomization | 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. | Some subjects did not have post-intervention prostate tissue that can be used for IHC analysis, therefore, the overall number of participants analyzed for IHC analysis is different from the total enrolled subjects. | Posted | Mean | Standard Error | percent positive | Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated |
|
|
|
| Primary | Expression of Histone Deacetylase 6 (HDAC6) | 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. | Some subjects did not have post-intervention prostate tissue that can be used for IHC analysis, therefore, the overall number of participants analyzed for IHC analysis is different from the total enrolled subjects. | Posted | Mean | Standard Error | H-score | Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated |
|
|
|
| 0 |
| 50 |
| 0 |
| 50 |
| 2 |
| 50 |
| EG001 | Placebo | Subjects in this group were administered with placebo. | 0 | 48 | 0 | 48 | 1 | 48 |
| Taste Alteration | Nervous system disorders | Non-systematic Assessment |
|
| Bloating | Gastrointestinal disorders | Non-systematic Assessment |
|
Not provided
Not provided