The Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study
Overview[ - collapse ][ - ]
Purpose | 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. |
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Condition | Familial Adenomatous Polyposis |
Intervention | Drug: metformin |
Phase | Phase 2 |
Sponsor | Yonsei University |
Responsible Party | Yonsei University |
ClinicalTrials.gov Identifier | NCT01725490 |
First Received | October 31, 2012 |
Last Updated | July 8, 2013 |
Last verified | July 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | October 31, 2012 |
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Last Updated Date | July 8, 2013 |
Start Date | November 2012 |
Estimated Primary Completion Date | September 2015 |
Current Primary Outcome Measures | 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. |
Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
Brief Title | The Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study |
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Official Title | Not Provided |
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. |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 2 |
Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
Condition | Familial Adenomatous Polyposis |
Intervention | 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. |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 100 |
Estimated Completion Date | September 2015 |
Estimated Primary Completion Date | September 2015 |
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. |
Gender | Both |
Ages | 20 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: TAE IL KIM, MD 82-2-2228-1965 taeilkim@yuhs.ac |
Location Countries | Korea, Republic of |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01725490 |
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Other Study ID Numbers | 4-2012-0491 |
Has Data Monitoring Committee | No |
Information Provided By | Yonsei University |
Study Sponsor | Yonsei University |
Collaborators | Not Provided |
Investigators | Not Provided |
Verification Date | July 2013 |
Locations[ + expand ][ + ]
Department of Internal Medicine, Yonsei University College of Medicine | Seoul, Korea, Republic of, 120-752 Contact: TAE IL KIM, MD | 82-2-2228-1965 | taeilkim@yuhs.acNot yet recruiting |
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Department of Internal Medicine, Yonsei University College of Medicine | Seoul, Korea, Republic of, 120-752 Contact: TAE IL KIM, MD | 82-2-2228-1965 | taeilkim@yuhs.acRecruiting |