Rheumatoid Arthritis
Conditions
Brief summary
Metformin has been used clinically for over 50 years, as a glucose lowering agent. Direct and indirect anti-inflammatory effects of metformin have been reported in animal and clinical studies, and this effect is independent of its hypoglycemic effect. Animal studies showed that metformin decreased serum C-reactive protein (CRP) level in atherogenic rabbits and decreased proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF-α) in obese mice . Moreover, metformin also suppressed osteoclastogenesis ; this may partially result from decreased expression of inflammatory cytokines that promote osteoclastogenesis in the arthritic joint. The objective of this study is to evaluate the efficacy and safety of addition of metformin to standard disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis.
Interventions
DRUGMetformin
metformin 850 mg bid for RA patients with moderate to high disease activity provided by DAS-28 score greater than 3.2
methotrexate, leflunomide, hydroxychloroquine or sulfasalazine
DRUGPlacebo Oral Tablet
oral tablet
Sponsors
Future University in Egypt
Ain Shams University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
single blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients older than 18 years (of both sexes) diagnosed with rheumatoid arthritis according to ACR / EULAR 2010 criteria . * Patients with moderate to high disease activity (DAS - 28 . score greater than 3.2) * Patients received the standard therapy (i.e. one or more conventional DMARDs) for at least three months.
Exclusion criteria
* Known hypersensitivity to metformin. * Patients who have a prior diagnosis with diabetes mellitus. * Patients receive metformin for any other indications. * Patients with congestive heart failure. * Patients with a history of myocardial infarction. * Patients with severe anemia. * Patients with active infections or other inflammatory diseases. * Patients receiving biological therapy. * Pregnancy or lactation. * Patients with impaired liver functions. * Patients with impaired kidney functions (serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL in males and females respectively). * Patients with malignancies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| disease activity scale in 28 joints ( DAS-28) | 6 months | scale assessing severity of rheumatoid arthritis based on number of tender , swollen joints , ESR levels ,and patient self-assessment of his condition (global health assessment) . Whereas 28 describes the number of different joints including in the measurement :proximal interphalangeal joints (10 joints),metacarpophalangeal joints (10),wrists (2),elbows (2),shoulders (2),knees (2). DAS28 values range from 2 to 10 while higher values mean a higher disease activity. A DAS-28 value \< 2.6 corresponds to remission,value between 2.6 and 3.2 corresponds to a low disease activity, value between 3.2 and 5.1 corresponds to a moderate disease activity, and DAS28 value \>5.1 corresponds to a high disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C reactive protein levels | 6 months | blood samples will be withdrawn at baseline and after 3 and 6 months to evaluate serum levels of C reactive protein |
| The HAQ (Health Assessment Score) | 6 months | HAQ-DI (Health Assessment Score- Disability index), in which patients are asked to rate their capacity to perform 20 activities of daily living (ADL). Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section, The Standard Disability Index (DI) calculated as the sum of the scores for various subscales divided by the number of subscales responded to, and results in a score between 0 and 3.Whereas scores can be interpreted as: From 0 to 1: mild difficulties to moderate disability, 2: moderate, 3: severe to very severe disability. |
| serum adiponectin level | 6-months | blood samples will be withdrawn at baseline and after 3 and 6 months to evaluate serum adiponetin levels using ELISA kits |
| adverse effect incidence | 6 months | adverse effect will be reported by patients or their caregivers and recorded by investigator |
Countries
Egypt
Contacts
Primary ContactWalaa F EL-Baz
Outcome results
None listed