title: ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial.
abstract: 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.
  
  
  
  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.
  
  
  
  Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers.
  
  
  
  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.
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Drew
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Chin
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Gilpin
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Parziale
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Pond
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Madeline M
authors.initials: MM
authors.lastname: Schuck
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Stewart
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Flagg
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Rawlings
authors.affiliation: McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Carolan
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chung
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Colizzo
authors.affiliation: Broad Institute, Cambridge, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Freedman
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gala
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Garber
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Kedrin
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Khalili
authors.affiliation: The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
authors.affiliation: Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA.
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.affiliation: Eicosanoid Core Laboratory, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Norman S
authors.initials: NS
authors.lastname: Nishioka
authors.affiliation: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Richter
authors.affiliation: Section of Gastroenterology, Boston Medical Center, Boston, MA, USA.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Staller
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.|Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.|Broad Institute, Cambridge, MA, USA. achan@mgh.harvard.edu.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.|Division of Gastroenterology and Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, GRJ-825C, Boston, MA, 02114, USA. achan@mgh.harvard.edu.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D001900:Boston; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002985:Clinical Protocols; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011453:Prostaglandins / Q000652:urine; D065840:Protective Factors; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D016207:Cytokines; D018836:Inflammation Mediators; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D001241:Aspirin
keywords: Aspirin; Biomarker; Chemoprevention; Colorectal cancer