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

doi:10.1186/s13063-016-1744-z

Randomized Controlled Trial

. 2017 Feb 1;18(1):50.

doi: 10.1186/s13063-016-1744-z.

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

David A Drew^{1

2}, Samantha M Chin^{1

2}, Katherine K Gilpin^{1

2}, Melanie Parziale^{1

2}, Emily Pond^{1

2}, Madeline M Schuck^{1

2}, Kathleen Stewart², Meaghan Flagg³, Crystal A Rawlings³, Vadim Backman⁴, Peter J Carolan², Daniel C Chung², Francis P Colizzo 3rd², Matthew Freedman⁵, Manish Gala^{1

2}, John J Garber², Curtis Huttenhower⁶, Dmitriy Kedrin², Hamed Khalili^{1

2}, Douglas S Kwon³, Sanford D Markowitz⁷, Ginger L Milne⁸, Norman S Nishioka², James M Richter², Hemant K Roy⁹, Kyle Staller^{1

2}, Molin Wang^{6

10

11}, Andrew T Chan^{12

13

14

15

16}

Affiliations

¹ Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁴ McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
⁵ Broad Institute, Cambridge, MA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA.
⁸ Eicosanoid Core Laboratory, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
⁹ Section of Gastroenterology, Boston Medical Center, Boston, MA, USA.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹² Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹³ Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁴ Broad Institute, Cambridge, MA, USA. achan@mgh.harvard.edu.
¹⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁶ Division of Gastroenterology and Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, GRJ-825C, Boston, MA, 02114, USA. achan@mgh.harvard.edu.

PMID: 28143522
PMCID: PMC5286828
DOI: 10.1186/s13063-016-1744-z

Randomized Controlled Trial

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

David A Drew et al. Trials. 2017.

. 2017 Feb 1;18(1):50.

doi: 10.1186/s13063-016-1744-z.

Authors

Affiliations

¹ Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³ The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁴ McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
⁵ Broad Institute, Cambridge, MA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA.
⁸ Eicosanoid Core Laboratory, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
⁹ Section of Gastroenterology, Boston Medical Center, Boston, MA, USA.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹² Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹³ Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁴ Broad Institute, Cambridge, MA, USA. achan@mgh.harvard.edu.
¹⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. achan@mgh.harvard.edu.
¹⁶ Division of Gastroenterology and Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, GRJ-825C, Boston, MA, 02114, USA. achan@mgh.harvard.edu.

PMID: 28143522
PMCID: PMC5286828
DOI: 10.1186/s13063-016-1744-z

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.

Keywords: Aspirin; Biomarker; Chemoprevention; Colorectal cancer.

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Figures

**Fig. 1**
ASPIRED study timeline (Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) diagram)

**Fig. 2**
ASPIRED assessments and biospecimens. Overview of patient assessments and biospecimens collected in the ASPIRED trial for correlative science experiments. Participants are asked to provide relevant lifestyle and dietary histories via paper questionnaire. Anthropometric measurements are collected at each visit by study staff. In addition, participants provide urine, saliva, blood, stool, and tissue samples at both study visits

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References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. doi: 10.3322/caac.21332. - DOI - PubMed
1. Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer. 2016;16:173–86. doi: 10.1038/nrc.2016.4. - DOI - PMC - PubMed
1. Bibbins-Domingo, K. on behalf of the United States Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836–45. - PubMed
1. Neale JR, Dean BJ. Liquid chromatography-tandem mass spectrometric quantification of the dehydration product of tetranor PGE-M, the major urinary metabolite of prostaglandin E(2) in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871:72–7. doi: 10.1016/j.jchromb.2008.06.042. - DOI - PubMed
1. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84. doi: 10.1056/NEJMoa061355. - DOI - PubMed

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[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. doi: 10.3322/caac.21332. - DOI - PubMed

[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. doi: 10.3322/caac.21332. - DOI - PubMed

[3] Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer. 2016;16:173–86. doi: 10.1038/nrc.2016.4. - DOI - PMC - PubMed

[4] Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer. 2016;16:173–86. doi: 10.1038/nrc.2016.4. - DOI - PMC - PubMed

[5] Bibbins-Domingo, K. on behalf of the United States Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836–45. - PubMed

[6] Bibbins-Domingo, K. on behalf of the United States Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836–45. - PubMed

[7] Neale JR, Dean BJ. Liquid chromatography-tandem mass spectrometric quantification of the dehydration product of tetranor PGE-M, the major urinary metabolite of prostaglandin E(2) in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871:72–7. doi: 10.1016/j.jchromb.2008.06.042. - DOI - PubMed

[8] Neale JR, Dean BJ. Liquid chromatography-tandem mass spectrometric quantification of the dehydration product of tetranor PGE-M, the major urinary metabolite of prostaglandin E(2) in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871:72–7. doi: 10.1016/j.jchromb.2008.06.042. - DOI - PubMed

[9] Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84. doi: 10.1056/NEJMoa061355. - DOI - PubMed

[10] Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84. doi: 10.1056/NEJMoa061355. - DOI - PubMed

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

Affiliations

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

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