Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 2
- 主要终点
- Change of Total Urine SFN (Sulforaphane) Metabolites
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Men scheduled for a prostate biopsy
- •Age 21 years or older
- •Signed informed subject consent
排除标准
- •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
研究组 & 干预措施
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
干预措施: SFN-rich broccoli sprout extract capsules (Drug)
Placebo capsules
Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily
干预措施: Gelatin capsule containing microcrystalline cellulose. (Dietary Supplement)
结局指标
主要结局
Change of Total Urine SFN (Sulforaphane) Metabolites
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
未报告次要终点
研究者
Jackilen Shannon
Staff Scientist
Portland VA Medical Center