Effect of Metformin on Patients With Osteoarthritis

NCT05034029 | Unknown

• 1 other identifier: K-2021-001-02
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 5

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.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline and 3, 6, 12, 24 months follow up

Secondary Outcomes (4)

• 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 effusion-synovitis volume 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

Study Arms (2)

Metformin

EXPERIMENTAL

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.

Drug: Metformin hydrochloride sustained release tablets

Placebo

PLACEBO COMPARATOR

Placebo will administer the same as the experimental drug.

Drug: Placebo

Interventions

Metformin hydrochloride sustained release tablets DRUG

Oral

Metformin

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Guangzhou First People's Hospital: lead

Study Sites (5)

Foshan First People's Hospital

Foshan, Guangzhou, China

NOT YET RECRUITING

Guangzhou First People's Hospital

Guangzhou, 510180, China

RECRUITING

Liwan Central Hospital of Guangzhou

Guangzhou, 510282, China

NOT YET RECRUITING

Sun Yat-Sen Memorial Hospital

Guangzhou, 510282, China

NOT YET RECRUITING

Zhujiang Hospital

Guangzhou, 510282, China

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 35598008 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Central Study Contacts

Guangfeng Ruan, Doctor

CONTACT

13060627790; ruan1989.ok@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 5, 2021
• Study Start: August 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 6, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)