Methotrexate in Erosive Inflammatory Hand Osteoarthritis

NCT04579848 | Active Not Recruiting Phase 4

• 1 other identifier: DIA2020-01
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hand Osteoarthritis; Erosive Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Finger pain on a visual analogue scale

  Difference in self-reported finger joint pain previous 48 hours on a 0-100 mm scale at 6 months of treatment; higher value indicate worse outcome.

  6 months

Secondary Outcomes (25)

• Finger pain on a visual analogue scale

  Month 1, 3, 9 and 12.

• Thumb pain on a visual analogue scale

  Month 1, 3, 6, 9 and 12.

• Pain most painful finger joint on a visual analogue scale

  Month 1, 3, 6, 9 and 12.

• Patient-reported disease activity on a visual analogue scale

  Month 1, 3, 6, 9 and 12.

• Pain all joints on a visual analogue scale

  Month 1, 3, 6, 9 and 12.

Other Outcomes (11)

• Sub-study: biopsy of knee OA

  Month 6

• Sub-study: knee pain on a visual analogue scale

  Month 6

• Question about blinding

  Month 12

Study Arms (2)

Methotrexate

ACTIVE COMPARATOR

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.

Drug: Methotrexate Tablets; Drug: Folic Acid 1 MG

Placebo

PLACEBO COMPARATOR

3 capsules per week for two weeks, followed by 4 capsules the remaining weeks. Additional Folic acid 1mg prescribed daily.

Drug: Placebo; Drug: Folic Acid 1 MG

Interventions

Methotrexate Tablets DRUG

Methotrexate 2.5mg oral tablet.

Methotrexate

Placebo DRUG

Placebo capsule

Placebo

Folic Acid 1 MG DRUG

Folic acid

Methotrexate; Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Diakonhjemmet Hospital: lead
• Oslo University Hospital: collaborator

Study Sites (1)

Diakonhjemmet Hospital

Oslo, Norway

Location

Related Publications (1)

• 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.

  PMID: 39807424 DERIVED

MeSH Terms

Interventions

Methotrexate; Folic Acid

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tore K Kvien, MD, PhD

  Professor Em.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical placebo cannot be produced due to text, color and shape of methotrexate tablets. Thus, both placebo and methotrexate will be encapsulated to ensure blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior researcher, doctor

Model Details: An investigator-initiated, randomized, double-blinded, placebo-controlled, parallel-group, single-center, phase IV, superiority study, exploring the effect of methotrexate on pain, function and structural outcomes in erosive inflammatory hand osteoarthritis.

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: October 8, 2020
• Study Start: August 12, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)