ASPirin Intervention for the REDuction of Colorectal Cancer Risk

Not Applicable

Active, not recruiting

• Conditions: Colorectal Cancer
• Interventions: Drug: Placebo for Aspirin; Drug: Aspirin

• Registration Number: NCT02394769
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

This research study is investigating the use of aspirin as a potential chemopreventive agent to reduce risk of colorectal cancer

Detailed Description

This research study, is investigating the use of aspirin as a potential chemopreventive agent to reduce risk of colorectal cancer. Within the gastroenterology practice of Massachusetts General Hospital (MGH), we will conduct a prospective, double-blind, placebo-controlled, randomized clinical trial to measure the effects of daily low-dose (81 mg/day) and standard-dose (325 mg/day) aspirin on urine, plasma, stool, and tissue biomarkers associated with colorectal cancer.

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 neoplasia, yet there remains uncertainty surrounding its mode of action. Aspirin has already been established to reduce the risk of cardiovascular disease. Prospective studies as well as randomized clinical trials demonstrate that aspirin reduces the risk of precancerous polyps and colorectal cancer.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-03-16
• Study First Submitted QC: 2015-03-16
• Study First Posted: 2015-03-20
• Study Start: 2015-07-06
• Primary Completion: 2019-04-11
• Results First Submitted: 2021-01-29
• Results First Submitted QC: 2021-02-28
• Results First Posted: 2021-03-23
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-19
• Last Update Posted: 2024-03-21
• Study Completion: 2029-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

• Underwent screening or surveillance colonoscopy at MGH within the last 9 months with removal of at least one adenoma.
• Age 18-80 years.
• 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. Patients over age 80 will not be enrolled since the benefits and risks of a daily aspirin regimen over the age of 80 have not yet been well-characterized.
• 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.

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Exclusion Criteria

• 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (For Aspirin)	Placebo for Aspirin	The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose, once daily, until the final visit. Duration not to exceed 12 weeks.
Low Dose Aspirin	Aspirin	The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (81 mg/d), once daily, until the final visit. Duration not to exceed 12 weeks.
Standard Dose Aspirin	Aspirin	The first dose of the study medication will be given to patients after the initial flexible sigmoidoscopy (start of randomization). Participants will be expected to take one capsule orally at the blinded dose (325mg/d), once daily, until the final visit. Duration not to exceed 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Urinary Prostaglandin Metabolites (PGE-M)	8-12 weeks	Measured using liquid chromatography/mass spectrometry

Secondary Outcome Measures

Name	Time	Method
Plasma Macrophage Inhibitory Cytokine-1 (MIC-1), an Inflammatory Biomarker	8-12 weeks	Measured using an ELISA for MIC-1
Chromatin Binding	8-12 weeks	Measured using ChIP-Seq of DNA extracted from colonic epithelium
Expression of Wnt-associated Signaling Genes (CTNNB1, AXIN2 and MYC)	8-12 weeks	Measured using RNA-seq of colonic epithelium
Spectral Biomarkers of Colorectal Cancer	8-12 weeks	Measured using Partial Wave Spectroscopy on rectal cytology brushing samples

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States