Clinical trial NCT00272324: Aspirin/Folate Prevention of Large Bowel Polyps
Official title: Aspirin/Folate Prevention of Large Bowel Polyps
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer
Polyps
Adenomas
Keywords: Colorectal neoplasms
Adenomatous polyps
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-05
Enrollment: 1121
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: This is a randomized controlled trial of aspirin and/or folate supplementation for the prevention of the recurrence of neoplastic polyps (adenomas) of the large bowel.

Detailed description: This is a randomized controlled trial of aspirin and/or folate supplementation for the prevention of the recurrence of neoplastic polyps (adenomas) of the large bowel among subjects with a recent history of these tumors. The study is a randomized, double-blind, placebo-controlled trial with a 2 x 3 factorial design.

Eligibility criteria: Inclusion Criteria:

1. One neoplastic polyp removed within three months of study entry or within 16 months of study entry if over 1 cm in size or if subject has had a lifetime history of at least two polyps, with the entire large bowel seen by colonoscopy to be free of further polyps within 3 months of entry.
2. An ability and willingness to follow the study protocol, as indicated by the subject's giving informed consent to participate.
3. Good general health, with no severely debilitating diseases or active malignancy that might compromise the patient's ability to complete the study.
4. Anticipated colonoscopic follow-up three years after the qualifying colonoscopy.
5. Age between 21 and 80 years at the time of the intake colonoscopy.
6. For women of childbearing potential, agreement to use effective birth control for the duration of the study.
7. Intent not to take aspirin or aspirin-containing products, NSAIDs or folic acid for the length of the study unless required by a physician.
8. Not randomized previously or currently in a chemoprevention trial, except for the: "Nutritional Prevention of Large Bowel Polyps" Study (Polyps Prevention Study I); and brief participation in the "VA Cooperative Study" with no continuing involvement.

Exclusion Criteria:

1. Invasive carcinoma in any colonic polyp removed.
2. Familial colonic polyposis syndromes.
3. Ulcerative colitis or Crohn's disease.
4. Malabsorption syndrome (e.g. pancreatic insufficiency).
5. Large bowel resection for any reason.
6. Diagnosed narcotic or alcohol dependence
7. Contraindication to aspirin use, including:

   1. documented peptic ulcer disease in the past 20 years
   2. aspirin sensitivity
   3. bleeding diathesis, including hemorrhagic stroke
8. Likelihood of NSAID use

   1. recurring arthritis or other musculo-skeletal problems
   2. frequent NSAID use in 5 years preceding
   3. history of stroke or TIAs
   4. history of angina or myocardial infarction
   5. desire to take aspirin for the prevention of cardiovascular disease
9. Required or contraindicated folic acid use pernicious anemia or folic acid deficiency
10. Pregnancy or lactation.

Primary outcomes:
measure: 1 or more adenomas
timeFrame: For aspirin: follow-up years 1-3; For folate: follow-up years 1-3 and years 4-8
Secondary outcomes:
measure: number of adenomas
timeFrame: For aspirin: follow-up years 1-3; For folate: follow-up years 1-3 and years 4-8
measure: 1 or more advanced lesions
timeFrame: For aspirin: follow-up years 1-3; For folate: follow-up years 1-3 and years 4-8
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Kaiser
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Detroit
country: United States
facility: Henry Ford Health Sciences Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: John A Baron, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003 Mar 6;348(10):891-9. doi: 10.1056/NEJMoa021735.
citation: Figueiredo JC, Passarelli MN, Wei W, Ahnen DJ, Morris JS, Corley L, Mehta T, Bartley AN, McKeown-Eyssen G, Bresalier RS, Barry EL, Goel A, Hernandez Mesa G, Hamilton SR, Baron JA. Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions. PLoS One. 2021 Nov 11;16(11):e0258878. doi: 10.1371/journal.pone.0258878. eCollection 2021.
citation: Passarelli MN, Mott LA, Barry EL, Rees JR, Baron JA. Oral Antibiotics and Risk of New Colorectal Adenomas During Surveillance Follow-up. Cancer Epidemiol Biomarkers Prev. 2021 Oct;30(10):1974-1976. doi: 10.1158/1055-9965.EPI-21-0323. Epub 2021 Jul 21.
citation: Passarelli MN, Barry EL, Rees JR, Mott LA, Zhang D, Ahnen DJ, Bresalier RS, Haile RW, McKeown-Eyssen G, Snover DC, Cole BF, Baron JA. Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial. Am J Clin Nutr. 2019 Oct 1;110(4):903-911. doi: 10.1093/ajcn/nqz160.
citation: Passarelli MN, Barry EL, Rees JR, Mott LA, Ahnen DJ, Baron JA. Body Composition and Aspirin Dose for Colorectal Adenoma Prevention in a Randomized Clinical Trial. Cancer Epidemiol Biomarkers Prev. 2019 Jul;28(7):1262-1265. doi: 10.1158/1055-9965.EPI-19-0205.
citation: Fedirko V, McKeown-Eyssen G, Serhan CN, Barry EL, Sandler RS, Figueiredo JC, Ahnen DJ, Bresalier RS, Robertson DJ, Anderson CW, Baron JA. Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas. Mol Carcinog. 2017 Aug;56(8):1977-1983. doi: 10.1002/mc.22629. Epub 2017 Mar 6.
citation: Yip WK, Bonetti M, Cole BF, Barcella W, Wang XV, Lazar A, Gelber RD. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis for continuous, binary, and count outcomes. Clin Trials. 2016 Aug;13(4):382-90. doi: 10.1177/1740774516643297. Epub 2016 Apr 19.
citation: Hazra A, Selhub J, Chao WH, Ueland PM, Hunter DJ, Baron JA. Uracil misincorporation into DNA and folic acid supplementation. Am J Clin Nutr. 2010 Jan;91(1):160-5. doi: 10.3945/ajcn.2009.28527. Epub 2009 Nov 18.
citation: Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER; Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9. doi: 10.1001/jama.297.21.2351.