Methotrexate Treatment in Hand Osteoarthritis Refractory to Usual Treatments (ADEM2)

Methotrexate Treatment in Hand Osteoarthritis Refractory to Usual Treatments: A Randomised, Double-blind, Placebo-controlled Trial

Randomized study comparing the structural efficacy of methotrexate versus placebo in digital osteoarthritis

Study Overview

• Status: Not yet recruiting
• Conditions: Erosive Hand Osteoarthritis
• Intervention / Treatment: Drug: Methotrexate Injectable Solution; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Christian ROUX, Pr; Phone Number: +33 492035512; Email: roux.c@chu-nice.fr

Study Locations

• France
  • Nice, France, 06000
    • CHU de Nice
    • Contact: Yacine ALLAM, Dr; Phone Number: +33 492035477; Email: allam.y@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Digital osteoarthritis (IPD and IPP) according to ACR criteria (with an X-ray of the hands taken less than 3 months ago, showing at least 3 joints with digital osteoarthritis KL>=2) and symptomatic for more than three months

Exclusion Criteria:

• Having a bilirubin level > 5 mg/dl (85.5 µmol/l)
• Pregnant or breastfeeding women (a urine pregnancy test will be performed on women of childbearing age),
• Injection of hyaluronic acid within the previous 6 months,
• Injection of cortisone derivatives within the previous 3 months,
• Presence of psoriasis,
• Inflammatory rheumatism,
• Microcrystalline arthropathy,
• Joint prosthesis in one of the joints of the hand,
• Planned placement of a joint prosthesis in the hand during the study period,
• Major progressive disease (life-threatening cardiovascular disease, hematopoietic cancers including myeloma, cancers with risk of bone metastases),
• Liver failure.
• Severe renal failure (creatinine clearance less than 50 ml/min).
• Positive hepatitis B serology.
• Tuberculosis, hepatitis C, HIV positive, or other immunodeficiency syndromes.
• Uncontrolled infections.
• Use of corticosteroids.
• Use of morphine derivatives,
• Taking Bactrim,
• Taking high doses of aspirin (greater than or equal to 500mg/day),
• Contraindications to the use of methotrexate,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The placebo consists of a 0.9% solution of sodium chloride (NaCl) in sterile distilled water for injection. This solution was chosen as the placebo. Injection every week during 12 month.
Active Comparator: Methotrexate injectable	Drug: Methotrexate Injectable Solution; Injection of methotrexate every week during 12 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural lesion	The progression of structural damage between M0 and M12, the worsening of digital osteoarthritis in a joint, will be defined by the change in stage of the Verbruggen-Veys score. The Verbruggen-Veys anatomical scoring system for hand osteoarthritis, which evaluates the radiographic progression of interphalangeal joints. This scale classifies each joint into five stages (N, S, J, E, R) reflecting increasing severity of structural damage. Progression is defined as a transition to a more advanced stage between M0 and M12. As this is a categorical ordinal scale rather than a continuous numerical score, there are no minimum or maximum numerical values. However, higher stages correspond to more severe structural damage and thus a worse outcome.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Function	Hand function will be assessed using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). The AUSCAN is a validated patient-reported outcome measure that evaluates pain, stiffness, and physical function in hand osteoarthritis. The function subscale consists of 9 items, each scored on a Likert scale. The total function score ranges from 0 to 36, with higher scores indicating worse functional impairment. Changes in the AUSCAN function score between baseline (M0) and 12 months (M12) will be analyzed.	12 months
Effectiveness of the treatment on pain	The effectiveness of the treatment on pain will be assessed using a Visual Analog Scale (VAS) for pain, a validated patient-reported outcome measure. The VAS consists of a 100 mm horizontal line, where 0 mm indicates "no pain" and 100 mm indicates "worst imaginable pain". The outcome will be expressed as the mean pain score (in millimeters) and the change in pain score from baseline (M0) at each time point (M3, M9, and M12). Higher scores indicate greater pain intensity and therefore a worse outcome.	12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Yacine ALLAM, Dr, Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Estimated): May 2, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 21-API-03; 2022-502362-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No