Clinical trial NCT00512850: Folic Acid in Preventing Colorectal Polyps in Patients With Previous Colorectal Polyps
Official title: The Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) Folic Acid Prevention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adenoma of Large Intestine
Keywords: Folic acid
Adenoma of Large Intestine
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Dana-Farber/Brigham and Women's Cancer Center
First posted: 2007-08-08
Enrollment: 672
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: RATIONALE: Chemoprevention is the use of certain substances to keep cancer from forming. The use of folic acid may prevent colorectal cancer.

PURPOSE: This randomized clinical trial is studying how well folic acid works compared with a placebo in preventing colorectal polyps in patients who have had previous colorectal polyps.

Detailed description: OBJECTIVES:

Primary

* Determine if folic acid supplementation lowers the adenoma recurrence rate.

Secondary

* Determine the number of adenomas per patient and the size and histology of the adenoma.
* Assess the interaction between folic acid and alcohol, methionine, and aspirin intake.
* Assess the interaction between folic acid and pretrial and midtrial folate levels.
* Assess other complementary biomarkers such as DNA methylation and blood folate level as risk factors for polyp recurrence.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral folic acid once daily.
* Arm II: Patients receive oral placebo once daily. At least 1 year after beginning treatment, patients are sent a blood collection kit in order to measure plasma vitamin B12 levels, to measure folate to assess compliance.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Participated in the Nurses' Health Study (NHS I) or the Health Professionals Follow-Up Study (HPFS) and have had a previous confirmed diagnosis of adenomatous polyp of the colon or rectum
* Plan on having an endoscopy within 4 years after initiation of the trial
* Must release medical records regarding past and any future endoscopies

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Plasma vitamin B12 concentration of ≥ 300 pg/mL or have a vitamin B12 concentration between 200 and 299 pg/mL and a methylmalonic acid (MMA) level ≤ 32 µg/L

Exclusion criteria:

* Diagnosis of cancer other than non-melanoma skin cancer, or early stage breast or prostate cancer
* Diagnosis of homocystinemia
* Diagnosis of pernicious anemia
* Any gastrointestinal disorder that could lead to a vitamin B12 deficiency
* Diagnosis of cirrhosis or pancreatitis
* Diagnosis of epilepsy, Alzheimer's disease, Parkinsonism, and psychiatric disorders that may interfere with normal functioning

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

* No prior gastrectomy, total colectomy, or pancreatectomy
* Other concurrent multivitamins or supplements that contain folic acid (they may take specific supplements, such as A, C, E, calcium, and iron, or antioxidant formula vitamins)
* No concurrent methotrexate or anticonvulsant

Primary outcomes:
measure: Recurrent colorectal adenoma
timeFrame: May 1996-March 2004
Secondary outcomes:
measure: recurrent adenoma by location, size, stage, number,
timeFrame: May1996-March 2004
Other outcomes:
Locations:
Study officials:
affiliation: Dana-Farber/Brigham and Women's Cancer Center
name: Edward L. Giovannucci, MD, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu K, Platz EA, Willett WC, Fuchs CS, Selhub J, Rosner BA, Hunter DJ, Giovannucci E. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. Am J Clin Nutr. 2009 Dec;90(6):1623-31. doi: 10.3945/ajcn.2009.28319. Epub 2009 Oct 28.
citation: Figueiredo JC, Mott LA, Giovannucci E, Wu K, Cole B, Grainge MJ, Logan RF, Baron JA. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int J Cancer. 2011 Jul 1;129(1):192-203. doi: 10.1002/ijc.25872. Epub 2011 Apr 1.