Clinical trial NCT05034029: Effect of Metformin on Patients With Osteoarthritis
Official title: Effect of Metformin on Tibiofemoral Cartilage Volume and Knee Symptoms Among Overweighted Knee Osteoarthritis patients-a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteoarthritis
Lead sponsor: Guangzhou First People's Hospital
Sponsor class: OTHER
First posted: 2021-09-05
Enrollment: 262
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change of tibiofemoral cartilage volume from baseline to 24 months follow up
timeFrame: Baseline and 24 months follow up
measure: Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up
timeFrame: Baseline and 3, 6, 12, 24 months follow up
Secondary outcomes:
measure: Change of knee pain visual analog scale from baseline to 24 months follow up
timeFrame: Baseline and 3, 6, 12, 24 months follow up
measure: Change of tibiofemoral cartilage defect from baseline to 24 months follow up
timeFrame: Baseline and 24 months follow up
measure: Change of effusion-synovitis volume from baseline to 24 months follow up
timeFrame: Baseline and 24 months follow up
measure: Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up
timeFrame: Baseline and 24 months follow up
Other outcomes:
Locations:
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangzhou
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
city: Guangzhou
country: China
facility: Liwan Central Hospital of Guangzhou
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital
city: Guangzhou
country: China
facility: Zhujiang Hospital
Study officials:
References:
citation: Ruan G, Yuan S, Lou A, Mo Y, Qu Y, Guo D, Guan S, Zhang Y, Lan X, Luo J, Mei Y, Zhang H, Wu W, Dai L, Yu Q, Cai X, Ding C. Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial. BMC Musculoskelet Disord. 2022 May 21;23(1):486. doi: 10.1186/s12891-022-05434-2.