ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): A study protocol for a randomized controlled trial

David A. Drew, Samantha M. Chin, Katherine K. Gilpin, Melanie Parziale, Emily Pond, Madeline M. Schuck, Kathleen Stewart, Meaghan Flagg, Crystal A. Rawlings, Vadim Backman, Peter J. Carolan, Daniel C. Chung, Francis P. Colizzo, Matthew Freedman, Manish Gala, John J. Garber, Curtis Huttenhower, Dmitriy Kedrin, Hamed Khalili, Douglas S. KwonSanford D. Markowitz, Ginger L. Milne, Norman S. Nishioka, James M. Richter, Hemant K. Roy, Kyle Staller, Molin Wang, Andrew T. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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 (81mg/day) or standard-dose (325mg/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 on16 March 2015.

Original languageEnglish (US)
Article number50
JournalTrials
Volume18
Issue number1
DOIs
StatePublished - Feb 1 2017

Keywords

  • Aspirin
  • Biomarker
  • Chemoprevention
  • Colorectal cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

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