Metformin Efficacy and Safety for Gastric Intestinal Metaplasia

Metformin Efficacy and Safety for Gastric Intestinal Metaplasia: a Randomized Controlled Trial

Gastric intestinal metaplasia significantly increases the risk of gastric cancer. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. The investigators devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against gastric intestinal metaplasia and the safety of this drug in non-diabetic gastric intestinal metaplasia patients.

Study Overview

• Status: Completed
• Conditions: Gastric Intestinal Metaplasia
• Intervention / Treatment: Drug: Metformin; Drug: Folate

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hosipital of Digestive Disease
    • Xi'an, Shaanxi, China
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged from 18 to 75 years old;
2. Body mass index (BMI) ranged from 18.5 to 23.9 at enrollment;
3. IM patients with OLGIM stage Ⅱ-Ⅲ diagnosed by upper gastrointestinal endoscopy and histopathological biopsy within the last 3 months;
4. Patients without H. pylori infection confirmed by 13C-urea breath test (UBT) or patients with H. pylori infection who completed the bismuth-containing quadruple program and had confirmed successful eradication by 13C-UBT.

Exclusion Criteria:

1. History of diabetes mellitus (use of medication and/or HbA1c over 6.5%);
2. History of regular use (defined as at least once per week) of NSAIDs and/or aspirin;
3. History of stomach surgery (including endoscopic submucosal dissection and endoscopic mucosal resection) or previously diagnosed malignant tumor;
4. History of heart failure, renal failure, liver cirrhosis or chronic hepatic failure;
5. Patients with contraindications or allergies to the drugs in this study;
6. Breastfeeding or pregnancy;
7. History of substance abuse or alcohol abuse in the past 1 year;
8. Severe mental illness;
9. Refusal of drug treatment;
10. Refusal of signing informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the metformin group; Patients in the metformin group shall receive oral metformin at 500 mg per day for 6 months.	Drug: Metformin; Subjects will be instructed to take one tablet(500mg) of metformin after breakfast every day, and to visit the hospital every 4 weeks for evaluation of the subjective symptoms and for receiving a new supply of medication.; Other Names: Glucophage
Active Comparator: the folate group; Patients in the folate group shall receive oral folate at 5 mg three times a day for 6 months.	Drug: Folate; Subjects will be instructed to take one tablet(5mg) of folate three times every day, and to visit the hospital every 4 weeks for evaluation of the subjective symptoms and for receiving a new supply of medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of reversal and progression of gastric intestinal metaplasia	To evaluate the effects of the therapies, each subject was assigned a stage score before the therapy (A) and at the end point (B) according to OLGIM stages.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of reversal and progression of gastric atrophy	To evaluate the effects of the therapies, each subject was assigned a stage score before the therapy (A) and at the end point (B) according to OLGA stages.	6 months
Fasting blood glucose	Fasting blood glucose in mg/dL.	6 months
Fasting blood insulin	Fasting blood insulin in μU/mL.	6 months
HbA1c	HbA1c in a percentage form.	6 months
Total cholesterol	Total cholesterol in mg/dL.	6 months
LDL-cholesterol	LDL-cholesterol in mg/dL.	6 months
Blood urea nitrogen (BUN)	Blood urea nitrogen (BUN) in mg/dL.	6 months
Creatinine	Creatinine in mg/dL.	6 months
physical examination findings	Physical examination findings included weight in kilograms, height in meters and weight and height will be combined to report body mass index (BMI) in kg/m^2.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of gastric mucosal bile acid profile in metformin group before the therapy and at the end point.	Investigators evaluate the changes of gastric mucosal bile acid profile in metformin group before the therapy and at the end point according to the results of UPLC-MS/MS and pathological.	6 months
Changes of gastric microbiota in metformin group before the therapy and at the end point.	Investigators explore the changes of gastric microbiota in metformin group before the therapy and at the end point according to the results of 16s rRNA sequencing.	6 months

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases
• Investigators: Study Director: Yongquan Shi, PhD, Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 20, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metaplasia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: KY20212212-C-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No