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

Sponsor

Yonsei University (Other)

Overall Status

Completed

CT.gov ID

NCT01725490

Collaborator

(none)

Enrollment

Location

Arms

90.4

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Familial Adenomatous Polyposis	Drug: Metformin Drug: Metformin Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Actual Study Start Date :

Feb 15, 2013

Actual Primary Completion Date :

Aug 30, 2020

Actual Study Completion Date :

Aug 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
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)	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.

Arm

Intervention/Treatment

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

Placebo Comparator: an identical- appearing placebo (arm C)

Drug: Placebo

Outcome Measures

Primary Outcome Measures

the mean percentage change of the number and size of polyps in colon and/or duodenum. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

FAP patients who had a history of colectomy within the previous 12 months or need to undergo colectomy within 8 months after randomization.
FAP patients with malignant disease, including colorectal cancer.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Internal Medicine, Yonsei University College of Medicine	Seoul		Korea, Republic of	120-752

Sponsors and Collaborators

Yonsei University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yonsei University

ClinicalTrials.gov Identifier:

NCT01725490

Other Study ID Numbers:

4-2012-0491

First Posted:

Nov 12, 2012

Last Update Posted:

Sep 20, 2021

Last Verified:

Sep 1, 2021

Keywords provided by Yonsei University

chemoprevention, metformin, familial adenomatous polyposis

Additional relevant MeSH terms:

Adenomatous Polyposis Coli

Metformin

Study Results

No Results Posted as of Sep 20, 2021