ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 161
- 试验地点
- 1
- 主要终点
- Change of ISC marker gene expression
研究概览
简要总结
This research study is studying a drug intervention as a possible chemoprevention strategy for colorectal cancer.
The name of the study intervention involved in this study is:
- Low Dose Aspirin
详细描述
This is prospective, double-blind, placebo-controlled, randomized clinical trial to measure the effects of daily low-dose (81 mg/day) aspirin on tissue, urine, plasma, and stool biomarkers associated with colorectal cancer with a focus on the effect of age. It is a direct extension of an earlier study: ASPIRED trial NCT02394769
Aspirin is part of the non-steroidal anti-inflammatory drug (NSAID) family, which are drugs routinely used for their pain-killing (analgesic), fever-reducing (antipyretic), or anti-inflammatory properties. Most NSAIDs are available as over-the-counter formulations. Substantial evidence has conclusively demonstrated that aspirin reduces the risk of colorectal polyps and cancer, yet there remains uncertainty surrounding its mode of action. Aspirin may prevent colorectal cancer through multiple interrelated biological mechanisms including the reduction of chronic inflammation, a known risk factor for colorectal cancer. Aspirin has been shown to directly affect prostaglandins, a class of biologic molecules that play important roles in controlling the normal inflammatory responses within your body. The exact mechanism by which aspirin acts to prevent colorectal cancer is still unknown.This study is looking at the mechanisms of aspirin's anti-cancer effect, which may lead to the discovery of novel specific characteristics (markers) that can be used to select patients for aspirin treatment. the study will also look at the effect age may have on these mechanisms.
The research study procedures include screening for eligibility and study treatment and scheduling two clinical research visits immediately before and after intervention with the study drug.
Participants will be randomized into two groups.
- Arm A: Daily Placebo (no aspirin) for the duration of the study.
- Arm B: Daily low dose aspirin (81 mg/day) for the duration of the study.
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
- Double (Participant, Investigator)
盲法说明
Double-Blinded
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have undergone screening or surveillance colonoscopy with removal of at least one adenoma within the last 9 months.
- •Age greater than or equal to 18 years and less than 55 years or greater than or equal to 65 years at the time of enrollment This study will only include adult participants because colorectal carcinogenesis in children is more likely to be related to a cancer predisposition syndrome with distinct biological mechanisms compared with sporadic colorectal cancer in adults.
- •ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
- •Not currently taking aspirin (any dose) within the last 6 months.
- •The effects of aspirin on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Use of any non-aspirin non-steroidal anti-inflammatory drug (NSAID) at any dose at least three times a week during the two months prior to randomization.
- •Diagnosis of inflammatory bowel disease, liver or kidney disease, bleeding diathesis.
- •Any prior diagnosis of gastrointestinal cancer (including esophageal, small intestine, colon, pancreatic), or any diagnosis of other cancers (with the exception of non-melanoma skin) in which there has been any active treatment within the last three years.
- •Participants who are receiving any other investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to aspirin.
- •Known diagnosis of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch Syndrome).
- •Any adenoma that was not completely removed during previous colonoscopy.
- •History of aspirin intolerance, bleeding diathesis, peptic ulcer or gastrointestinal bleed, endoscopic complications, or contraindication to colonoscopy.
- •Inability or unwillingness to abstain from non-protocol use of aspirin or NSAIDs or to provide blood, urine, or stool samples or colon biopsies during the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or breastfeeding. Pregnant women are excluded from this study because aspirin is an FDA Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with aspirin, breastfeeding should be discontinued if the mother is treated with aspirin.
- •Participant must be able to swallow pills.
- •Participant is taking any anticoagulant agent (e.g. warfarin) or antiplatelet agent (e.g. clopidogrel).
研究组 & 干预措施
Placebo
Participants will be randomly assigned to placebo group and receive a daily placebo capsule for the duration of the study up to 12 weeks.
干预措施: Placebo (Other)
Low Dose Aspirin
Participants will be randomly assigned to aspirin group and receive a daily low dose aspirin (81 mg) for the duration of the study up to 12 weeks.
干预措施: Aspirin (Drug)
结局指标
主要结局
Change of ISC marker gene expression
时间窗: 2 months
Assess the difference in the change of ISC marker using scRNA-seq data analysis
次要结局
- Change in Urinary PGE-M(2 months)
- Change in urinary Plasma GDF-15(2 months)
- ChIP-seq Analysis of Colonic Epithelium(2 months)
- Gene Expression Analysis of Colonic Epithelium(2 months)
- Change in Microbiome(2 months)
研究者
Andrew T. Chan, MD, MPH
Principal Investigator
Massachusetts General Hospital