Methotrexate in Erosive Inflammatory Hand Osteoarthritis

NCT ID: NCT04579848

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-12
• Study Completion Date: 2026-12-31

Brief Summary

A placebo-controlled randomized controlled trial exploring the effect of methotrexate on pain, function and structural outcomes in erosive inflammatory hand osteoarthritis.

Detailed Description

The trial will include Norwegian adult males and females with symptomatic erosive inflammatory hand osteoarthritis.

Participants will be randomized 1:1 to either:

1. Methotrexate oral x 1/week; weekly starting dose 15 mg for two weeks, followed by 20 mg the remaining weeks (intervention group). Dosage can be reduced to as low as 10 mg if higher doses are not tolerated.

2. Placebo (control group).

Both arms will receive folic acid 1mg daily.

The treatment duration for both groups is 52 weeks.

Conditions

Hand Osteoarthritis; Erosive Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Methotrexate

Methotrexate oral x 1/week; weekly starting dose 15 mg for two weeks, followed by 20 mg the remaining weeks.

Additional Folic acid 1mg prescribed daily.

Group Type: ACTIVE_COMPARATOR

Methotrexate Tablets

Intervention Type: DRUG

Methotrexate 2.5mg oral tablet.

Folic Acid 1 MG

Intervention Type: DRUG

Folic acid

Placebo

3 capsules per week for two weeks, followed by 4 capsules the remaining weeks.

Additional Folic acid 1mg prescribed daily.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule

Folic Acid 1 MG

Intervention Type: DRUG

Folic acid

Interventions

Methotrexate Tablets

Methotrexate 2.5mg oral tablet.

Intervention Type: DRUG

Placebo

Placebo capsule

Intervention Type: DRUG

Folic Acid 1 MG

Folic acid

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Finger joint pain 40-80 on 0-100 visual analog scale (VAS) with insufficient pain relief from, inability to tolerate or contra-indications to oral paracetamol and/or NSAIDs, and hand symptoms (pain, aching, or stiffness) on most days the previous 6 weeks before randomization.
• Hand OA according to the American College of Rheumatology (ACR) criteria, at least 1 distal (DIP) or proximal interphalangeal (PIP) joint of the 2nd-5th finger with radiographic pre-erosive (J-phase) or erosive disease (E-phase) according to the Verbruggen-Veys anatomical phase system, and at least two DIP/PIP joints with power Doppler signal of at least grade 1 or grey-scale synovitis of at least grade 2 on ultrasound.

Exclusion Criteria

• Contraindications to methotrexate:

• Abnormal renal function, defined as serum creatinine >142 µmol/L in women and >168 µmol/L in men, or a glomeruli filtration rate (GFR) <40 mL/min/1.73 m2.
• Abnormal liver function, defined as transaminases above the upper normal limit, active or previous hepatitis B or C infection, or known cirrhosis
• Lung fibrosis (maximum 6 months old x-ray), active infection, or reduced hematopoiesis (i.e. anemia, leukopenia and/or thrombocytopenia).
• Planned pregnancy within 18 months after screening (men/women), and pregnancy, breastfeeding, or insufficient anti-conception therapy for female fertile participants. Contraception should be maintained during treatment and until the end of systemic exposure, i.e. 3 months after methotrexate discontinuation. Sufficient anti-conception therapy consists of intra-uterine device (coil) or hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections).
• Alcohol or other drug abuse in the last year.
• Intolerance to lactose.
• Chronic inflammatory rheumatic diseases (such as rheumatoid arthritis and psoriatic arthritis or gout), active inflammatory bowel disease, or positive rheumatoid factor or anti-CCP antibodies.
• Other severe co-morbidities such as hemochromatosis, fibromyalgia, psoriasis, blood dyscrasias, and coagulation disorders, history of malignancy (except successfully treated squamous or basal cell skin carcinoma), uncontrolled diabetes mellitus, severe hypertension, unstable ischemic heart disease, severe heart failure, severe pulmonary disease, severe and/or opportunistic infections and/or chronic infections, active tuberculosis, positive human immunodeficiency virus (HIV) status, recent stroke, bone marrow hypoplasia, or demyelinating diseases of the central nervous system.
• Other likely causes of hand symptoms: thoracic outlet syndrome, carpal tunnel disease, diabetic cheiropathy, injury in finger joints previous 6 months, or palmar tenosynovitis/trigger finger.
• Oral or intra-muscular steroids in the previous month
• Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before inclusion
• Analgesics or NSAIDs, unless stable dosage for ≥1 month.
• Symptomatic slow-acting drugs for OA (SYSADOA), unless stable dose for ≥3 months and require stable dose throughout the study.
• Disease-modifying osteoarthritis drugs (DMOADs) previous three months.
• Scheduled hand surgery during study participation.
• Planning to start other treatments for hand OA in the study participation period.
• Not able to adhere to the study visit schedule and protocol requirements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Diakonhjemmet Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ida Kristin Haugen

Senior researcher, doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tore K Kvien, MD, PhD

Role: STUDY_CHAIR

Professor Em.

Locations

Diakonhjemmet Hospital

Oslo, , Norway

Countries

Norway

References

Mathiessen A, Gaundal L, Sexton J, Sjolie D, Steen Pettersen P, Slatkowsky-Christensen B, Haugen IK. Protocol for the MERINO study: A randomized placebo-controlled trial assessing the efficacy, safety, and cost-effectiveness of methotrexate in people with erosive hand osteoarthritis. Osteoarthr Cartil Open. 2024 Dec 15;7(1):100558. doi: 10.1016/j.ocarto.2024.100558. eCollection 2025 Mar.

Reference Type: DERIVED

PMID: 39807424 (View on PubMed)

Study Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

DIA2020-01

Identifier Type: -

Identifier Source: org_study_id