Role of Methotrexate in Ultrasound Proven Synovitis in Primary Knee OA

Summary

Background:

Osteoarthritis (OA) is a leading cause of disability worldwide, with limited treatment options and many patients suffering from chronic pain. Modern imaging has revealed that OA involves complex changes in cartilage, subchondral bone, and synovium. Pain in OA is often linked to synovitis, which is common in the condition. Methotrexate (MTX), a proven treatment for synovitis in inflammatory arthritis like rheumatoid arthritis and has a well-known safety profile. The proposal suggests that using MTX may have potential to treat symptomatic knee OA with USG (musculoskeletal ultrasound) proven synovitis by reducing synovitis and as a result, alleviate pain.

Objectives:

To assess the role of methotrexate in primary knee osteoarthritis associated with ultrasound proven synovitis.

Methods:

This randomized Controlled trial will be conducted in the department of Rheumatology, Bangladesh Medical University (BMU) from July 2025 to June 2026. A total of 70 patients will be enrolled with primary knee OA diagnosed on the basis of ACR Criteria for Knee OA with informed written consent. MSK USG examinations of knee joint and scoring (OMERACT SCORE) will be performed to detect synovitis by a rheumatologist expert in MSK US. Then randomization will be done into group A and group B following a randomization table, each consisting of 35 patients. Consecutive sampling techniques will be followed. One group will receive MTX (start with 15 mg per week for the first 2 weeks then increase to 20 mg and continue for the remaining period if tolerated) and Both groups of patients will be allowed to take NSAIDs on a requirement basis with documentation and follow non-pharmacological treatment of OA. At the end of 3rd and 6th month pain and functional status will be assessed by WOMAC, VAS and quality of life will be assessed by using Bangla version of SF-12. At the end of 6th month improvement of synovitis will be seen by MSK USG of involved knees with OMERACT scoring. Primary endpoint for efficacy will be assessed at the end of 24th week by WOMAC. Secondary endpoints will be determined by VAS and SF-12. Adverse effects will be assessed by history, physical examinations and investigations. The data will be analyzed by using the latest version SPSS software (Version 29). Results will be recorded using means and standard deviations. Results will be compared among two groups with a 95% confidence interval and a p- value of \< 0.05 will be considered statistically significant. The degrees of statistical significance between groups will be analyzed by unpaired t test (for quantitative normally distributed data) and Mann Whitney U test if there is skewed distribution. Qualitative data in between groups will be analyzed by the chi square test. Probabilities of associations will be assessed by calculating Pearson's rank correlation coefficient. P-value \<0.05 will be regarded as statistically significant. The nature, purpose and implication of the study as well as the entire spectrum of benefits and risks of study will be explained to the patients. Privacy and confidentiality of the subject will be maintained. Each patient will enjoy the right to participate and or withdraw from the study at any point of the study period. Ethical clearance will be obtained from the institutional Review Board (IRB) of BMU.

Conditions

• Osteo Arthritis of the Knee
• Synovitis of Knee
• Methotrexate

Interventions

DRUG

Methotrexate (MTX)

One group will receive MTX, starting with 15 mg per week for the first 2 weeks then increase to 20 mg and continue for the remaining period if tolerated. another group will receive placebo

DRUG

Placebo

The investigational drug and the placebo will be formulated to be identical in appearance, packaging, labeling. Blinded study medications will be prepared, packaged, and labeled by the sponsor according to Good Manufacturing Practice (GMP) standards. All packaging will use neutral labeling with unique subject numbers only.

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  lead OTHER

Principal Investigators

• Shamim Ahmed Professor, FCPS · Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-30

Primary Completion

2026-07-01

Completion

2026-08-30

Countries

• Bangladesh

Study Locations