Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Genome-wide expression analyses using RNA-Seq
研究概览
简要总结
The goal of this study is to investigate that a common cholesterol lowering agent (atorvastatin) alone or combining with a nonsteroidal anti-inflammatory drug (aspirin) would reduce the risk of colorectal cancer (CRC) in high-risk individuals with Lynch syndrome.
详细描述
This is an exploratory biomarker trial to assess the ability of atorvastatin (common cholesterol lowering agent) alone or combining with aspirin (a nonsteroidal anti-inflammatory drug) to reduce the risk of colorectal cancer in high-risk individuals with Lynch Syndrome. Subjects will be stratified based on their prior history of polyps/cancer to receive atorvastatin without or with aspirin for 6 weeks. Blood and normal colon biopsies will be obtained at Day 0 and at 6 weeks on study. Tissue endpoints for analysis include cell proliferation, apoptosis and changes in gene expression. Circulating lipid profiles and metabolic function, and post-treatment questionnaires will be used to assess the acceptability of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who are 18 years of age or older
- •Able to read and sign an informed consent document in English
- •Eligible subjects will have molecular evidence of Lynch Syndrome (mutation in MLH1, MSH2, MSH6, EPCAM or PMS2)
- •History of colorectal cancer if surgically cured and > 1 year from completion of adjuvant chemotherapy
排除标准
- •Are <18 years of age
- •Unable to read and sign an informed consent document in English
- •Have active cancer or are less than 3 years post hormonal maintenance therapy for cancer
- •Have statin intolerance or contraindication for aspirin or atorvastatin use
- •Are pregnant or are actively breast feeding
研究组 & 干预措施
Atorvastatin
Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks
干预措施: Atorvastatin 20mg (Drug)
Atorvastatin and Aspirin
Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks
干预措施: Atorvastatin 20mg AND Aspirin 325 mg (Drug)
结局指标
主要结局
Genome-wide expression analyses using RNA-Seq
时间窗: Changes from baseline to 6 weeks
Effect of Atorvastatin or/and Aspirin on gene expressions in normal colonic epithelial cells will be analyzed using RNA-Seq. Total RNA will be extracted from frozen biopsies. RNASeq libraries will be generated and sequenced on an Illumina platform and analyzed. Differential expression between samples at baseline and 6-weeks of drug treatment will be assessed for statistical significance. Genes with false discovery rat ≤ 0.05 and a fold-change ≥ 2 will be considered significant.
Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining
时间窗: Changes from baseline to 6 weeks
Effect of Atorvastatin or/and Aspirin on normal colonic proliferation and apoptosis will be evaluated by comparing of immunohistochemical staining of Ki-67 and active caspase 3 using formalin-fixed paraffin-embedded biopsies collected before and at the 6 weeks of drug treatments. Number of positive cells and total number of evaluated cells will be collected for both assays. Data of cells with positive Ki-67 or active caspase 3 will be expressed as % of positive cells (# positive cells/#total evaluated cells x 100). Statistical analyses will be performed to compare the difference between baseline and 6-weeks data.
次要结局
- Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).(6 weeks)
- Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks(6 weeks)
- Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.(6 weeks)