Effect of Metformin on Tibiofemoral Cartilage Volume and Knee Symptoms Among Overweighted Knee Osteoarthritis patients-a Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 262
- 试验地点
- 5
- 主要终点
- Change of tibiofemoral cartilage volume from baseline to 24 months follow up
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis assessed by a rheumatologist;
- •Age 50 to 75 years;
- •Body mass index ≥ 24 kg/m2;
- •Knee pain ≥ 20 on a 100 mm visual analogue scale (VAS);
- •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.
排除标准
- •Severe radiographic knee OA as grade 3 joint space narrowing according to the Osteoarthritis Research Society International (OARSI) atlas;
- •Severe knee pain as knee pain ≥ 80 on a 100 mm VAS;
- •Planned knee or hip surgery (including arthroscopy, joint replacement, and joint open operation) within 2 years;
- •Severe knee trauma history (including arthroscopy, severe injury of knee ligament or meniscus);
- •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);
- •Other forms of inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis);
- •Active malignant cancer or other life-threatening diseases;
- •Type 1 or type 2 diabetes mellitus;
- •Clinical manifestation of liver dysfunction or alanine aminotransferase/aspartate aminotransferase exceeding 2 times the upper limit of normal value;
- •Estimated glomerular filtration rate less than 60 ml/min/1.73 m2;
- •Hypoxic state (e.g. chronic heart insufficiency, acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, cor pulmonale, peripheral vascular disease);
- •Alcoholism;
- •Pregnancy or lactation;
- •Allergic to metformin hydrochloride;
- •Conditions affecting the absorption of oral drugs (e.g. postgastrectomy and malabsorption syndrome);
- •Use of metformin in recent 30 days or plan to use metformin in the next 2 years;
- •Use of investigational drug in recent 30 days.
研究组 & 干预措施
Metformin
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.
干预措施: Metformin hydrochloride sustained release tablets (Drug)
Placebo
Placebo will administer the same as the experimental drug.
干预措施: Placebo (Drug)
结局指标
主要结局
Change of tibiofemoral cartilage volume from baseline to 24 months follow up
时间窗: Baseline and 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.
Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up
时间窗: Baseline and 3, 6, 12, 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.
次要结局
- Change of knee pain visual analog scale from baseline to 24 months follow up(Baseline and 3, 6, 12, 24 months follow up)
- Change of tibiofemoral cartilage defect from baseline to 24 months follow up(Baseline and 24 months follow up)
- Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up(Baseline and 24 months follow up)
- Change of effusion-synovitis volume from baseline to 24 months follow up(Baseline and 24 months follow up)