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

NCT ID: NCT01725490

Last Updated: 2021-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-15
• Study Completion Date: 2020-08-30

Brief Summary

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.

Conditions

Familial Adenomatous Polyposis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

metformin 500mg daily (arm A)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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.

metformin 1500mg daily (arm B)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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.

an identical- appearing placebo (arm C)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Internal Medicine, Yonsei University College of Medicine

Seoul, , South Korea

Countries

South Korea

References

Park JJ, Kim BC, Hong SP, Seo Y, Lee HS, Park YS, Na SY, Park SC, Park J, Kim JH, Moon CM, Huh KC, Park SJ, Cheon JH, Kim WH, Kim TI. The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis. Cancer Prev Res (Phila). 2021 May;14(5):563-572. doi: 10.1158/1940-6207.CAPR-20-0580. Epub 2021 Jan 28.

Reference Type: DERIVED

PMID: 33509804 (View on PubMed)

Other Identifiers

4-2012-0491

Identifier Type: -

Identifier Source: org_study_id