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

Primary Purpose

Familial Adenomatous Polyposis

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Metformin
Metformin
Placebo
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Adenomatous Polyposis focused on measuring chemoprevention, metformin, familial adenomatous polyposis

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Internal Medicine, Yonsei University College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

metformin 500mg daily (arm A)

metformin 1500mg daily (arm B)

an identical- appearing placebo (arm C)

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
October 31, 2012
Last Updated
September 16, 2021
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT01725490
Brief Title
The Chemopreventive Effect of Metformin in Patients With Familial Adenomatous Polyposis: Double Blinded Randomized Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
February 15, 2013 (Actual)
Primary Completion Date
August 30, 2020 (Actual)
Study Completion Date
August 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Adenomatous Polyposis
Keywords
chemoprevention, metformin, familial adenomatous polyposis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
metformin 500mg daily (arm A)
Arm Type
Experimental
Arm Title
metformin 1500mg daily (arm B)
Arm Type
Experimental
Arm Title
an identical- appearing placebo (arm C)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
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
Intervention Name(s)
Metformin
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
the mean percentage change of the number and size of polyps in colon and/or duodenum.
Description
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.
Time Frame
After seven-month administration of metformin/placebo, colonoscopy/sigmoidoscopy and upper gastrointestinal endoscopy will be performed.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Department of Internal Medicine, Yonsei University College of Medicine
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
33509804
Citation
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.
Results Reference
derived

Learn more about this trial

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

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