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

Yonsei University

Status and phase: Completed; Phase 2

Conditions: Familial Adenomatous Polyposis

Treatments: Drug: Placebo; Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT01725490

4-2012-0491

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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34 participants in 3 patient groups, including a placebo group

metformin 500mg daily (arm A)

Experimental group

Treatment:

Drug: Metformin

Drug: Metformin

metformin 1500mg daily (arm B)

Experimental group

Treatment:

Drug: Metformin

Drug: Metformin

an identical- appearing placebo (arm C)

Placebo Comparator group

Treatment:

Drug: Placebo