NCT04196868

Methotrexate and Metformin in Rheumatoid Arthritis Patients

Randomized Placebo-controlled Trial Comparing Methotrexate vs. Methotrexate/Metformin Association in Rheumatoid Arthritis Patients

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 128 (actual)
• Sponsor: University Hospital, Bordeaux · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Methotrexate (MTX) is the anchor drug for patients with rheumatoid arthritis (RA). Despite its marked efficacy and acceptable side effect profile, about 1/3 of patients failed to reach RA remission. Metformin is the first-line therapy for type 2 diabetes. Its antioxidative and anti-inflammatory properties make it a good candidate for the treatment of inflammatory diseases such as rheumatoid arthritis.

Detailed description

Methotrexate is usually the first-line disease modifying antirheumatic drugs (DMARD) for the treatment of RA. The main goal of its treatment is to reach disease remission but, despite its good efficacy, 1/3 of patients failed to achieve it. This could lead to the introduction of a biologic therapy which is more expensive and exposes the patient to a greater infection risk. Neutrophils through expulsion of neutrophil extracellular traps (NETs), were found to be important in RA pathogenesis (source of anti-citrullinated protein antibodies, activation of fibroblast-like synoviocytes…). The formation of NETs is reactive oxygen species (ROS) dependent, while metformin can selectivity inhibit mitochondrial respiratory chain complex I and decrease NADPH oxidase activity, thus leading to a decrease in ROS production. Metformin is the first-line therapy for type 2 diabetes. Recently, a study presented its potential impact in the treatment of systemic lupus erythematosus according to its metabolic properties and the inhibition of NETosis. The aim of this study is to compare the efficacy of Methotrexate/Metformin vs. Methotrexate alone on the decrease of RA activity in MTX-naive patients, after 6 months of treatment.

Conditions

• Arthritis, Rheumatoid

Interventions

Type	Name	Description
DRUG	Metformin treatment	1500 mg once a day, per os, during six months
OTHER	Placebo	per os, during six months
DRUG	Methotrexate treatment	per os

Timeline

• Start date: 2020-12-03
• Primary completion: 2024-12-19
• Completion: 2026-06-01
• First posted: 2019-12-12
• Last updated: 2026-02-03

Locations

12 sites across 1 country: France