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Arthritis, RheumatoidPhase 2METorMET²NCT04196868

Methotrexate and Metformin in Rheumatoid Arthritis Patients

A Phase 2 study testing Metformin treatment and Methotrexate treatment in people with Arthritis, Rheumatoid, run by University Hospital, Bordeaux at 12 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
Metformin treatment and Methotrexate treatment
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
128 participants
Where
12 sitesFrance
Study dates
3 Dec 2020to 16 Jun 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • OR
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  • 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
  • Having signed an informed consent form (later than the day of inclusion and before any examination required by the research)

Who cannot join

  • Patient who present contraindications to treatment with Methotrexate or Metformin
  • Patient with type 1 or type 2 diabetes
  • Patient with daily corticosteroid treatment at a dosage ≥ 15 mg/day within four weeks before the inclusion
  • 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
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  • 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
  • B12 Vitamin deficiency
  • Patient performing or planning to perform a long-fasting period
  • Pregnant or breastfeeding women
  • Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

France12 sites

  • CH de la Côte Basque - service de rhumatologie

    Bayonne

  • CHU de Bordeaux - service de rhumatologie

    Bordeaux

  • CHU de Brest - service de rhumatologie

    Brest

  • CH de Cahors - service de rhumatologie

    Cahors

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

    Caluire-et-Cuire

  • CHD de Vendée - service de rhumatologie

    La Roche-sur-Yon

  • CH du Mans - service de rhumatologie

    Le Mans

  • CH de Libourne - service de rhumatologie

    Libourne

  • CHU de Montpellier - service de rhumatologie

    Montpellier

  • CHR Orléans la Source - service de rhumatologie

    Orléans

  • CH de Pau - service de rhumatologie

    Pau

  • CHU de Toulouse - service de rhumatolgie

    Toulouse

Other trials in France

About this study

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

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.

Read the 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.

Being tested
Metformin treatment, Placebo, Methotrexate treatment
Keywords
rheumatoid arthritis, methotrexate, metformin, clinical trial
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metformin treatmentDrug

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

  • PlaceboOther

    per os, during six months

  • Methotrexate treatmentDrug

    per os

Study groups in NCT04196868
Study groupRoleWhat they receive
Experimental armExperimentalNot described
Receives: Drug: Metformin treatment; Drug: Methotrexate treatment
Control armPlacebo comparatorNot described
Receives: Other: Placebo; Drug: Methotrexate treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of level of RA activity according to Disease Activity Score on 28 joints (DAS28-CRP)

    Measured: At baseline (Day 0) and 6 months after baseline

Secondary outcomes (14)

  1. Proportion of patients who reach remission

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

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

    Measured: At 6 months after baseline (Day 0)

  3. Proportion of patients for which a biologic treatment is introduced

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

  4. Mean dosage of Methotrexate in the two groups of randomization

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

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

    Measured: At 6 months after baseline (Day 0)

  6. Evolution of functional assessment according to Health Assessment Questionnaire (HAQ) within the two groups

    Measured: At baseline (Day 0), 1 month, 3 months, 6 months, 12 months and 24 months after baseline

  7. Mean value of weight in kilograms in each randomization group

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

  8. Mean value of waist circumference in centimeters in each randomization group

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

  9. Mean value of fasting glycemia in g/l in each randomization group

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

  10. Mean value of hemoglobin A1c level (HbA1c) in percentage in each randomization group

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

  11. Mean value of cholesterol levels and triglycerides levels in g/l in each randomization group

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

  12. Mean value of insulinemia in µUI/ml in each randomization group

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

  13. Mean value of bilirubin in mg/l in each randomization group

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

  14. Secondary Outcome Measures " : Change of level of RA according to Disease Activity Score on 28 joints (DAS28-ESR)

    Measured: At baseline (Day 0), 1 month, 3 months, 6 months, 12 months and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2019
  2. Study start3 Dec 2020
  3. Primary completion19 Dec 2024
  4. Study completion16 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04196868
Sponsor's protocol ID
CHUBX 2016/44
Other IDs
2024-511033-35-00, 2018-004287-56, 2018
Acronym
METorMET²
Status last verified
Sep 2026
First submitted
5 Dec 2019
Last updated
9 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin treatment and Methotrexate treatment in people with Arthritis, Rheumatoid, run by University Hospital, Bordeaux at 12 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of level of RA activity according to Disease Activity Score on 28 joints (DAS28-CRP) (time frame: At baseline (Day 0) and 6 months after baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04196868.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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