The Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2013 by Yonsei University.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
Yonsei University Identifier:
First received: October 31, 2012
Last updated: July 8, 2013
Last verified: July 2013
Familial adenomatous polyposis (FAP) leads to adenomas and eventual adenocarcinomas in colon and less frequently, duodenum. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas and cancers. The non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitor have shown the regression of colorectal and duodenal adenomas in FAP patients. However, these drugs showed gastrointestinal damage and cardiovascular risks, and new preventive strategies are needed. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggested to have a suppressive effect on tumorigenesis via mTOR-inhibiting pathway, and have no significant safety issues in long term use. The investigators devised a double-blind randomized controlled trial to evaluate the effect of metformin on polyps of colorectum and duodenum in non-diabetic FAP patients.

Condition Intervention Phase
Familial Adenomatous Polyposis
Drug: metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • the mean percentage change of the number and size of polyps in colon and/or duodenum. [ Time Frame: After seven-month administration of metformin/placebo, colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy will be performed. ]
    At the base-line endoscopy, India-ink tattoo will be placed in the ascending colon, sigmoid colon/rectum, and duodenum. In case of patient with retained rectum after colectomy and ileorectal anastomosis, sigmoidoscopy will be performed. The base-line and seven-month endoscopic examination will be recorded, and photographs will be taken at the tattoo-marked area and used for measurements of the number and size of polyps. The diameter of a polyp will be measured with the aid of biopsy forceps included in the photographic field, and only distinct polyps at least 2 mm in diameter will be counted.

Estimated Enrollment: 100
Study Start Date: November 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: metformin 500mg daily (arm A) Drug: metformin
Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.
Experimental: metformin 1500mg daily (arm B) Drug: metformin
Patients will be randomly assigned in a 2:2:1 ratio to receive metformin or identical-appearing placebo tablets orally for 7 months: metformin 500mg once and placebo twice a day in arm A, metformin 500mg three times a day in arm B, and placebo three times a day in arm C.
Placebo Comparator: an identical- appearing placebo (arm C)


Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with familial adenomatous polyposis(FAP) who are 20 to 65 years of age.
  2. FAP patients who have colonic or duodenal polyp
  3. FAP patients who have five or more polyps 2mm or more in diameter in endoscopic examination.

Exclusion Criteria:

  1. FAP patients who had a history of colectomy within the previous 12 months or need to undergo colectomy within 8 months after randomization.
  2. FAP patients with malignant disease, including colorectal cancer.
  3. FAP patients who used NSAIDs (non-steroidal anti-inflammatory drugs) or aspirin three or more times a week within 6 months of randomization. 4. FAP patients with diabetes mellitus. 5. Pregnant or breast-feeding patients. 6. Patients with abnormal results of serum laboratory tests (renal function and liver function test) and significant infectious or respiratory diseases.
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Please refer to this study by its identifier: NCT01725490

Korea, Republic of
Department of Internal Medicine, Yonsei University College of Medicine
Seoul, Korea, Republic of, 120-752
Sponsors and Collaborators
Yonsei University
  More Information

Responsible Party: Yonsei University Identifier: NCT01725490     History of Changes
Other Study ID Numbers: 4-2012-0491 
Study First Received: October 31, 2012
Last Updated: July 8, 2013

Keywords provided by Yonsei University:
chemoprevention, metformin, familial adenomatous polyposis

Additional relevant MeSH terms:
Adenomatous Polyposis Coli
Adenomatous Polyps
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Intestinal Polyposis
Genetic Diseases, Inborn
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on January 19, 2017