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

study id #: NCT01725490

condition: Familial Adenomatous Polyposis

status: Status unknown

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.

intervention: Drug: metformin

start date: November 2012

estimated completion: September 2015

last updated: July 8, 2013

phase of development: Phase 2

size / enrollment: 100

study design:
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

primary outcomes:

• 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. ] [ Designated as safety issue: No ]
  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.

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.

sponsor: Yonsei University

contacts:
TAE IL KIM, MD
82-2-2228-1965
taeilkim@yuhs.ac

locations: Republic of Korea