Effect of Metformin on Patients With Osteoarthritis

Guangzhou First People's Hospital

Status: Enrolling

Conditions: Osteoarthritis

Treatments: Drug: Metformin hydrochloride sustained release tablets; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05034029

K-2021-001-02

Details and patient eligibility

About

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.

Enrollment: 262 estimated patients

Sex: All

Ages: 50 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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262 participants in 2 patient groups, including a placebo group

Metformin

Experimental group

Description:

Metformin hydrochloride sustained release tablet will administer orally in escalating doses to reduce side-effects and maintain masking: 0.5 g/day for the first two weeks, 1 g/day for the next 2 weeks, and then 2 g/day until the end of the study if tolerated. If the subject cannot tolerate the maximum dose (2 g/day), take their maximum tolerable dose. In case of adverse reaction, the researchers can determine whether the subject needs to reduce or stop the drug based on their discretion.

Treatment:

Drug: Metformin hydrochloride sustained release tablets

Placebo

Placebo Comparator group

Description:

Placebo will administer the same as the experimental drug.

Treatment:

Drug: Placebo