Role of Methotrexate in Ultrasound Proven Synovitis in Primary Knee OA

NCT ID: NCT07161336

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-30

Study Completion Date

2026-08-30

Brief Summary

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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.

Detailed Description

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Conditions

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Osteo Arthritis of the Knee Synovitis of Knee Methotrexate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A Double blind randomized controlled trial study will be carried out in the outpatient department of rheumatology in BMU to determine the efficacy of Methotrexate in the treatment of primary knee OA associated with synovitis. Ethical approval will be taken from the Ethical Review Committee of BMU, Dhaka. At first, patients who attend the outpatient rheumatology department with knee pain will be requested to give verbal consent. Then, primary knee OA will be diagnosed by ACR clinical and radiological criteria, and subsequently, history, physical examination, and investigation will be done for evaluation of exclusion criteria. Then MSKUS examinations of knee joint and scoring (OMERACT SCORE) will be performed to detect synovitis by one rheumatologist experienced in MSK ultrasound using a MINDRAY machine with an 6-18 MHz linear array transducer operating at 3 MHz Power Doppler (PD) signal settings will be Pulse repetition frequency 750Hz, Doppler frequency 11.1 MHz, gain of 50% and low wa
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Methotrexate (MTX)

As it will be a double blinded study , the investigator and the patient is unable to know if the drug is MTX or placebo

Group Type ACTIVE_COMPARATOR

Methotrexate (MTX)

Intervention Type DRUG

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

Placebo

As it will be a double blinded study , the investigator and the patient is unable to know if the drug is MTX or placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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MTX Low dose Methotrexate

Eligibility Criteria

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Inclusion Criteria

* Men and women aged between 40 to 70 years
* Patients fulfilling American College of Rheumatology (ACR) clinical and radiological criteria for knee OA. (knee pain + at least 3 of 5 that not including "no palpable warmth")
* Knee pain on most days for at least 6 months, with a pain VAS of at least 40mm
* Radiological grading of OA with Kallgren-Lawrence grade of 2 to 3
* Patients with the presence of knee synovitis in Musculoskeletal ultrasound

Exclusion Criteria

* Any known inflammatory arthritis
* BMI \>= 40 kg/m2
* Abnormal renal (e.g. abnormal renal function Creatinine clearance \<35 ml) hepatic (including active hepatitis B, hepatitis C, abnormal liver function), hematological (e.g. white cell count \< 4 × 109/L, platelets \<100 ×109/L, or hemoglobin \< 9 g/dL), function
* Use of intra-articular, intramuscular or oral corticosteroids in previous 4 weeks
* History knee joint surgery, Charcot joint
* Severe valgus knee deformity (angle of genu valgum \> 30°)
* Use of any disease modifying agents (e.g. hydroxychloroquine or sulfasalazine) in previous 3 months
* Allergic to MTX
* Pregnant or lactating women
Minimum Eligible Age

40 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

OTHER

Sponsor Role lead

Responsible Party

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Akash Ahmed Alif

MD resident , Rheumatology department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shamim Ahmed Professor, FCPS

Role: STUDY_CHAIR

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Locations

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Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Dhaka, Dhaka Division, Bangladesh

Site Status RECRUITING

Countries

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Bangladesh

Central Contacts

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Akash Ahmed Alif, MBBS

Role: CONTACT

+8801726459070 ext. +8801825484701

Facility Contacts

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Akash Ahmed Alif

Role: primary

01726459070

Role: backup

Other Identifiers

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5535

Identifier Type: -

Identifier Source: org_study_id

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