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ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED)

We have recently published the protocol for the ASPIRED clinical trial that launched in Summer 2015 at MGH. The protocol can be found (open-access) here. Briefly, ASPIRED is a double-blind, placebo-controlled randomized clinical biomarker trial of aspirin at two doses in patients with a history of adenoma and is currently enrolling participants.

Abstract

Background

Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties.

Methods/design

ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function.

Discussion

Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers.

Trial registration

This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769. Registered on 16 March 2015.

New comprehensive review of aspirin chemoprevention of colorectal cancer.

I’m pleased to share the final product of a long-running project that I view as a great personal accomplishment. Our comprehensive review of aspirin chemoprevention entitled “Aspirin and colorectal cancer: the promise of precision chemoprevention” and co-authored with Dr. Yin Cao and Dr. Andrew T. Chan has been published as an Opinion article in Nature Reviews Cancer online and will appear in the March 2016 issue of the journal. To view the article please go to the Nature Reviews Cancer site or view it on PubMed (26868177).

ABSTRACT:

Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin’s mechanism of action.