Methotrexate and Metformin in Rheumatoid Arthritis Patients

NCT04196868 | Active Not Recruiting Phase 2

• 1 other identifier: CHUBX 2016/44
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Arthritis, Rheumatoid

Keywords

rheumatoid arthritis; methotrexate; metformin; clinical trial

Outcome Measures

Primary Outcomes (1)

• Change of level of RA activity according to Disease Activity score on 28 joints (DAS28-ESR)

  At baseline (Day 0) and 6 months after baseline

Secondary Outcomes (13)

• Proportion of patients who reach remission

  At 6 months, 12 months and 24 months after baseline (Day 0)

• Proportion of patients with low disease activity (DAS-ESR < 3,2)

  At 6 months after baseline (Day 0)

• Proportion of patients for which a biologic treatment is introduced

  At 6 months, 12 months and 24 months after baseline (Day 0)

• Mean dosage of Methotrexate in the two groups of randomization

  At 6 months, 12 months and 24 months after baseline (Day 0)

• Proportion of patients who present a serious adverse event within the two groups

  At 6 months after baseline (Day 0)

Study Arms (2)

Experimental arm

EXPERIMENTAL

Drug: Metformin treatment; Drug: Methotrexate treatment

Control arm

PLACEBO COMPARATOR

Other: Placebo; Drug: Methotrexate treatment

Interventions

Metformin treatment DRUG

1500 mg once a day, per os, during six months

Experimental arm

Placebo OTHER

per os, during six months

Control arm

Methotrexate treatment DRUG

per os

Control arm; Experimental arm

Eligibility Criteria

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

You may qualify if:

• Patients aged over 18 years old,
• Patient affected by RA according to American College of Rheumatology (ACR) 2010 criteria
• DAS28-ESR \> 3.2
• Methotrexate naïve patients, or without any methotrexate intake for more than six months.
• Men who accept to take active contraception during the study and during six months after the end of the Methotrexate treatment. Partner of patient will be informed of teratogenicity of MTX and will be advised to be on effective contraceptives for all the study duration.
• Women with a negative test of β-human chorionic gonadotropin (HCG) who accept to take active contraception during the study and during six months after the end of the Methotrexate treatment
• Patients without any Metformin previous therapy.
• Being affiliated to a health insurance system

You may not qualify if:

• Patient who present contraindications to treatment with Methotrexate or Metformin
• Patient with type 1 or type 2 diabetes
• History of allergy or intolerance to biguanide
• Presence of anemia (hemoglobin \< 80 g/l), neutropenia (neutrophils count \< 1500 mm3), lymphopenia (lymphocytes count \< 750 mm3), thrombopenia (platelets \< 100 000/mm3) or bone marrow hypoplasia.
• Renal insufficiency with clearance \< 50 ml/mn
• Decompensated heart failure
• Uncontrolled heart history
• Severe respiratory insufficiency
• Hepatic insufficiency, or bilirubin level upper than 5mg/dl (85,5 µmol/l), or aspartate transaminase (ASAT) / alanine aminotransferase (ALAT) more than twice the standard level.
• Acute or chronic infection, such as tuberculosis or HIV
• Critical ischemia of the lower limbs
• Recent stroke
• Patient with pleural effusion, or ascites
• Patient with stomatitis, mouth ulcers, or active gastrointestinal ulcer.
• Patient with alcohol intoxication

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Ministry for Health and Solidarity, France: collaborator

Study Sites (12)

CH de la Côte Basque - service de rhumatologie

Bayonne, France

Location

CHU de Bordeaux - service de rhumatologie

Bordeaux, France

Location

CHU de Brest - service de rhumatologie

Brest, France

Location

CH de Cahors - service de rhumatologie

Cahors, France

Location

Clinique de l'Infirmerie protestante de Lyon - service de rhumatologie

Caluire-et-Cuire, France

Location

CHD de Vendée - service de rhumatologie

La Roche-sur-Yon, France

Location

CH du Mans - service de rhumatologie

Le Mans, France

Location

CH de Libourne - service de rhumatologie

Libourne, France

Location

CHU de Montpellier - service de rhumatologie

Montpellier, France

Location

CHR Orléans la Source - service de rhumatologie

Orléans, France

Location

CH de Pau - service de rhumatologie

Pau, France

Location

CHU de Toulouse - service de rhumatolgie

Toulouse, France

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Christophe RICHEZ, Prof

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Antoine BENARD, MD, PhD

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: placebo-controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 12, 2019
• Study Start: December 3, 2020
• Primary Completion: December 19, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

FR (12)