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.
ConditionFamilial Adenomatous Polyposis
InterventionDrug: metformin
PhasePhase 2
SponsorYonsei University
Responsible PartyYonsei University
ClinicalTrials.gov IdentifierNCT01725490
First ReceivedOctober 31, 2012
Last UpdatedJuly 8, 2013
Last verifiedJuly 2013

Tracking Information[ + expand ][ + ]

First Received DateOctober 31, 2012
Last Updated DateJuly 8, 2013
Start DateNovember 2012
Estimated Primary Completion DateSeptember 2015
Current Primary Outcome Measuresthe 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 MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleThe Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study
Official TitleNot 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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionFamilial Adenomatous Polyposis
InterventionDrug: 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)
  • Experimental: metformin 500mg daily (arm A)
  • Experimental: metformin 1500mg daily (arm B)
  • Placebo Comparator: an identical- appearing placebo (arm C)

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment100
Estimated Completion DateSeptember 2015
Estimated Primary Completion DateSeptember 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.
GenderBoth
Ages20 Years
Accepts Healthy VolunteersNo
ContactsContact: TAE IL KIM, MD
82-2-2228-1965
taeilkim@yuhs.ac
Location CountriesKorea, Republic of

Administrative Information[ + expand ][ + ]

NCT Number NCT01725490
Other Study ID Numbers4-2012-0491
Has Data Monitoring CommitteeNo
Information Provided ByYonsei University
Study SponsorYonsei University
CollaboratorsNot Provided
Investigators Not Provided
Verification DateJuly 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.ac
Not yet recruiting
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.ac
Recruiting