Effect of Metformin on Patients With Osteoarthritis

Guangzhou First People's Hospital262 enrolled

Overview

This randomized controlled trial aims to investigate if metformin has osteoarthritis protective effects among overweighted knee osteoarthritis patients. The co-primary outcomes are changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Arthritis Index (WOMAC) from baseline to month 24. The secondary outcomes are changes in visual analog scale (VAS)-assessed knee pain, tibiofemoral cartilage defect, effusion-synovitis volume, and tibiofemoral bone marrow lesion maximum size from baseline to month 24.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

262

Conditions

Osteoarthritis

Interventions

Metformin hydrochloride sustained release tabletsDRUG

Oral

PlaceboDRUG

Placebo

Eligibility

Sex: ALLMin age: 50 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Meet the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis assessed by a rheumatologist; 2. Age 50 to 75 years; 3. Body mass index ≥ 24 kg/m2; 4. Knee pain ≥ 20 on a 100 mm visual analogue scale (VAS); 5. Able to listen, speak, read and understand Chinese; capable of understanding the study requirements and willing to cooperate with the study instructions; able to provide written, informed consent. Exclusion Criteria: 1. Severe radiographic knee OA as grade 3 joint space narrowing according to the Osteoarthritis Research Society International (OARSI) atlas; 2. Severe knee pain as knee pain ≥ 80 on a 100 mm VAS; 3. Planned knee or hip surgery (including arthroscopy, joint replacement, and joint open operation) within 2 years; 4. Severe knee trauma history (including arthroscopy, severe injury of knee ligament or meniscus); 5. Contraindication to MRI scanning (e.g. implanted pacemaker, artificial metal valve or cornea, aneurysm clipping surgery, arterial dissection, metal foreign bodies in the eyeball, claustrophobia); 6. Other forms of inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis); 7. Active malignant cancer or other life-threatening diseases; 8. Type 1 or type 2 diabetes mellitus; 9. Clinical manifestation of liver dysfunction or alanine aminotransferase/aspartate aminotransferase exceeding 2 times the upper limit of normal value; 10. Estimated glomerular filtration rate less than 60 ml/min/1.73 m2; 11. Hypoxic state (e.g. chronic heart insufficiency, acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, cor pulmonale, peripheral vascular disease); 12. Alcoholism; 13. Pregnancy or lactation; 14. Allergic to metformin hydrochloride; 15. Conditions affecting the absorption of oral drugs (e.g. postgastrectomy and malabsorption syndrome); 16. Use of metformin in recent 30 days or plan to use metformin in the next 2 years; 17. Use of investigational drug in recent 30 days.

Locations (5)

Foshan First People's Hospital

Foshan, Guangzhou, China

NOT_YET_RECRUITING

Guangzhou First People's Hospital

Guangzhou, China

RECRUITING

Liwan Central Hospital of Guangzhou

Guangzhou, China

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Change of tibiofemoral cartilage volume from baseline to 24 months follow up

Cartilage volume will be automatically calculated based on a standardized view of 3D cartilage geometry by OsiriX software (University of Geneva, Geneva, Switzerland). The 3D cartilage geometry is composed from the 2D cartilage shapes, which are generated by drawing contours around the cartilage boundaries on section-by-section MR images. Tibiofemoral cartilage volume will be calculated as the sum of both the tibial and femoral compartments.

Time frame: Baseline and 24 months follow up

Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up

The WOMAC system in a 100-mm visual analog format will be used to quantify the degree of knee pain (5 questions), joint stiffness (2 questions), and physical dysfunction (17 questions) during the last 7 days. The WOMAC score will be calculated by summing the score of each question (1 point for every 1 mm), and a higher score of WOMAC represents a severe OA symptom. The WOMAC score will be considered invalid and treated as missing data if more than 5 of the questions are not answered. In case no more than 5 items are missed, the remaining items will be averaged and then multiplied by 24 to create the WOMAC score.

Time frame: Baseline and 3, 6, 12, 24 months follow up

Secondary Outcomes

Change of knee pain visual analog scale from baseline to 24 months follow up

The 100 mm VAS will be used to assess the knee pain during the last 7 days, and a higher VAS indicates a severe knee pain.

Time frame: Baseline and 3, 6, 12, 24 months follow up

Change of tibiofemoral cartilage defect from baseline to 24 months follow up

Cartilage defects will be graded using a modified Outerbridge classification as follows: grade 0, normal cartilage; grade 1, focal blistering and intra-cartilaginous hyperintensity with a normal contour; grade 2, irregularities on the surface and loss of thickness of less than 50%; grade 3, deep ulceration with loss of thickness of more than 50% without exposure of subchondral bone; grade 4, full-thickness chondral wear with exposure of subchondral bone. Cartilage defects will be assessed at the medial tibial, medial femoral, lateral tibial, and lateral femoral compartments, and tibiofemoral cartilage defects will be obtained by summing the scores of the four compartments.

Central Contacts

Guangfeng Ruan, Doctor

CONTACT

13060627790 ruan1989.ok@163.com

Data from ClinicalTrials.gov

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