Metformin for the Prevention of CRA Recurrence

Study Overview
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Brief Summary
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Most of the sporadic colorectal cancer (CRC )develop from colorectal adenoma (CRA), patients with CRA have a high risk of recurrence and development of metachronous CRA or CRC after removal, therefore, the investigators conducted this clinical trial to explore the chemoprevetion effect of metformin for CRA recurrence after removal.

Detailed Description
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Colorectal adenomas are well-known to be precancerous lesions that develop into colorectal cancers on the basis of the adenoma-carcinoma sequence. The effects of screening for colorectal adenomas and removing precancerous lesions on the prevention of colorectal cancer have been established. Because of the high recurrence rates of colorectal adenomas in patients who have undergone polypectomy, the potential chemopreventive agents that may reduce the risk of colorectal adenoma recurrence need to be investigated. Metformin is a widely used diabetes medicine. In recent years, anticancer activity of metformin has been explored. The aim of this study is to investigate the effect of metformin on the recurrence of colorectal adenomas by conducting a randomized, placebo-controlled, prospective clinical.

Official Title
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The Role of Metformin in the Prevention for Colorectal Adenoma Recurrence in Post-polypectomy Patients

Conditions
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Colorectal Adenoma, Metformin, Chemoprevention

Intervention / Treatment
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* Drug: low-dose metformin
* Drug: high-dose metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 40-80 years without diabetes; CRAs removed without recurrence before recruitment; Must sign the consent form after being fully informed and understanding the purpose and procedure of this study. Exclusion Criteria: Familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome); Regularly taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase 2 (COX2) inhibitors, calcium or vitamin D; Have a history of gastrointestinal surgery; Have severe heart, liver or kidney disease ; Have cancer history; Women with pregnant, during breast-feeding period, or with expect pregnancy; Diabetes（taking diabetes medicines or HbA1c>6.5%); Inflammatory bowel disease; Mental illness; Intolerant to metformin; Cannot tolerate colonoscopy; Staffs in this clinical trial; Poor bowel preparation for colonoscopy or the examination time is shorter than 6 minutes; Unsuitable for inclusion by the investigator

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose metformin group<br>low-dose metformin, 250mg/day | Drug: low-dose metformin<br>* Metformin Pill 250mg/day<br>|
| Experimental: high-dose metformin group<br>high-dose metformin, 500mg/day | Drug: high-dose metformin<br>* Metformin Pill 500mg/day<br>|
| Placebo Comparator: control group<br>placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRA recurrence rate | Percentage of patients who has recurrence of CRA(colorectal adenoma) during or after chemotherapy with metformin or placebo. | one year, two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All polypoid lesions incidence rate | Percentage of patients who has incidence of all polypoid lesions during or after chemotherapy with metformin or placebo. | one year, two years | 
| CRC incidence rate | Percentage of patients who has incidence of CRC (colorectal cancer) during or after chemotherapy with metformin or placebo. | one year, two years |