Prostate Cancer PreventionPBroCNCT01265953
Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation
A study testing SFN-rich broccoli sprout extract capsules and Gelatin capsule containing microcrystalline cellulose. in people with Prostate Cancer Prevention, run by Portland VA Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Prostate Cancer Prevention
- What is being tested?
- SFN-rich broccoli sprout extract capsules and Gelatin capsule containing microcrystalline cellulose.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2011to Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men scheduled for a prostate biopsy
- Age 21 years or older
- Signed informed subject consent
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Portland VA Medical Center
Portland, Oregon, 97239
About this study
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.
Read the 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).
- Conditions
- Prostate Cancer Prevention
- Being tested
- SFN-rich broccoli sprout extract capsules, Gelatin capsule containing microcrystalline cellulose.
- Keywords
- cancer prevention, isothiocyanate, sulforaphane
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SFN-rich broccoli sprout extract capsulesDrug
Also called BSE, SFN, Sulforaphane
Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily
Gelatin capsule containing microcrystalline cellulose.Dietary supplement
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: SFN-rich broccoli sprout extract capsules |
| Placebo capsules | Placebo comparator | Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily Receives: Dietary Supplement: Gelatin capsule containing microcrystalline cellulose. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Baseline and 4-8 weeks following intervention; prostate biopsy were collected post-intervention when clinically-indicated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study startJul 2011
- Primary completionOct 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate Cancer PreventionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Portland VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- National Cancer Institute (NCI), Oregon State University, OHSU Knight Cancer Institute
- Responsible party
- Principal investigator, Jackilen Shannon, Portland VA Medical Center
- Investigators
- Jackilen Shannon, PhD, Principal investigator, Portland VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265953
- Sponsor's protocol ID
- Portland VA-09-0607
- Other IDs
- 2096, 6232, 2P01CA090890-06A2
- Acronym
- PBroC
- Status last verified
- Apr 2019
- First submitted
- 16 Dec 2010
- Last updated
- 1 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31155953
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation
- ClinicalTrials.gov ID
- NCT01265953
- Acronym / sponsor ID
- PBroC / Portland VA-09-0607
- Conditions
- Prostate Cancer Prevention
- Keywords
- cancer prevention, isothiocyanate, sulforaphane
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Portland VA Medical CenterUS federal agency
- Collaborators
- National Cancer Institute (NCI), Oregon State University, OHSU Knight Cancer Institute
- Study start
- Jul 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Posted 14 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SFN-rich broccoli sprout extract capsules | Experimental | Drug: SFN-rich broccoli sprout extract capsulesFour 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 | Dietary Supplement: Gelatin capsule containing microcrystalline cellulose.Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily |
Who may qualify
- Ages
- 21 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Men scheduled for a prostate biopsy
- Age 21 years or older
- Signed informed subject consent
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SFN-rich broccoli sprout extract capsulesAlso: BSE, SFN, SulforaphaneFour weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily | Drug | SFN-rich broccoli sprout extract capsules |
| Gelatin capsule containing microcrystalline cellulose.Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily | Dietary supplement | Placebo capsules |
Primary outcome
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
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
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31155953Zhang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jackilen Shannon, PhD principal investigator
Portland VA Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SFN-rich broccoli sprout extract capsules and Gelatin capsule containing microcrystalline cellulose. in people with Prostate Cancer Prevention, run by Portland VA Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Total Urine SFN (Sulforaphane) Metabolites (time frame: Baseline and 4-8 weeks following intervention). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01265953, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2019.