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

NCT01725490 | Completed Phase 2

• 1 other identifier: 4-2012-0491
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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

Keywords

chemoprevention, metformin, familial adenomatous polyposis

Outcome Measures

Primary Outcomes (1)

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

  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.

  After seven-month administration of metformin/placebo, colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy will be performed.

Study Arms (3)

metformin 500mg daily (arm A)

EXPERIMENTAL

Drug: Metformin

metformin 1500mg daily (arm B)

EXPERIMENTAL

Drug: Metformin

an identical- appearing placebo (arm C)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Metformin 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 500mg daily (arm A)

Placebo 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)

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Department of Internal Medicine, Yonsei University College of Medicine

Seoul, 120-752, South Korea

Location

Related Publications (1)

• 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.

  PMID: 33509804 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Interventions

Metformin

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2012
• First Posted: November 12, 2012
• Study Start: February 15, 2013
• Primary Completion: August 30, 2020
• Study Completion: August 30, 2020
• Last Updated: September 20, 2021

Record last verified: 2021-09

Locations

KR (1)