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

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

来源：Trials, 2017, 18(1): 50.

DOI：10.1186/s13063-016-1744-z

• Aspirin
• Colorectal cancer
• Biomarker
• Chemoprevention

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.

• 出版日期2017-2-1
• 单位MIT; 西北大学