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. Kwon; Sanford D. Markowitz; Ginger L. Milne; Norman S. Nishioka; James M. Richter; Hemant K. Roy; Kyle Staller; Molin Wang; Andrew T. Chan

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, 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

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

38 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 language	English (US)
Article number	50
Journal	Trials
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s13063-016-1744-z
State	Published - Feb 1 2017

Funding

ATC previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Aralaz Pharmaceuticals, and Pfizer Inc. HKR is a minority shareholder of Nanocytomics LLC and American BioOptics. SM has an unlicensed intellectual property patent covering use of HPGD to predict NSAID response. This study was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Aralaz Pharmaceuticals, Pfizer Inc., Nanycytomics LLC, or American BioOptics. No other competing interests exist. The other authors declare that they have no competing interests. ATC previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Aralaz Pharmaceuticals, and Pfizer Inc. HKR is a minority shareholder of Nanocytomics LLC and American BioOptics. SM has an unlicensed intellectual property patent covering use of HPGD to predict NSAID response. This study was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Aralaz Pharmaceuticals, Pfizer Inc., Nanocytomics LLC, or American BioOptics, No other competing interests exist. The other authors declare that they have no competing interests.

Keywords

Aspirin
Biomarker
Chemoprevention
Colorectal cancer

ASJC Scopus subject areas

Pharmacology (medical)
Medicine (miscellaneous)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13063-016-1744-z

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Drew, D. A., Chin, S. M., Gilpin, K. K., Parziale, M., Pond, E., Schuck, M. M., Stewart, K., Flagg, M., Rawlings, C. A., Backman, V., Carolan, P. J., Chung, D. C., Colizzo, F. P., Freedman, M., Gala, M., Garber, J. J., Huttenhower, C., Kedrin, D., Khalili, H., ... Chan, A. T. (2017). ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): A study protocol for a randomized controlled trial. Trials, 18(1), Article 50. https://doi.org/10.1186/s13063-016-1744-z

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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.",

keywords = "Aspirin, Biomarker, Chemoprevention, Colorectal cancer",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

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day = "1",

doi = "10.1186/s13063-016-1744-z",

language = "English (US)",

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Drew, DA, Chin, SM, Gilpin, KK, Parziale, M, Pond, E, Schuck, MM, Stewart, K, Flagg, M, Rawlings, CA, Backman, V, Carolan, PJ, Chung, DC, Colizzo, FP, Freedman, M, Gala, M, Garber, JJ, Huttenhower, C, Kedrin, D, Khalili, H, Kwon, DS, Markowitz, SD, Milne, GL, Nishioka, NS, Richter, JM, Roy, HK, Staller, K, Wang, M & Chan, AT 2017, 'ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): A study protocol for a randomized controlled trial', Trials, vol. 18, no. 1, 50. https://doi.org/10.1186/s13063-016-1744-z

TY - JOUR

T1 - ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED)

T2 - A study protocol for a randomized controlled trial

AU - Drew, David A.

AU - Chin, Samantha M.

AU - Gilpin, Katherine K.

AU - Parziale, Melanie

AU - Pond, Emily

AU - Schuck, Madeline M.

AU - Stewart, Kathleen

AU - Flagg, Meaghan

AU - Rawlings, Crystal A.

AU - Backman, Vadim

AU - Carolan, Peter J.

AU - Chung, Daniel C.

AU - Colizzo, Francis P.

AU - Freedman, Matthew

AU - Gala, Manish

AU - Garber, John J.

AU - Huttenhower, Curtis

AU - Kedrin, Dmitriy

AU - Khalili, Hamed

AU - Kwon, Douglas S.

AU - Markowitz, Sanford D.

AU - Milne, Ginger L.

AU - Nishioka, Norman S.

AU - Richter, James M.

AU - Roy, Hemant K.

AU - Staller, Kyle

AU - Wang, Molin

AU - Chan, Andrew T.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - Aspirin

KW - Biomarker

KW - Chemoprevention

KW - Colorectal cancer

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UR - http://www.scopus.com/inward/citedby.url?scp=85011256364&partnerID=8YFLogxK

U2 - 10.1186/s13063-016-1744-z

DO - 10.1186/s13063-016-1744-z

M3 - Article

C2 - 28143522

AN - SCOPUS:85011256364

SN - 1745-6215

VL - 18

JO - Trials

JF - Trials

IS - 1

M1 - 50

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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