The Effect of Metformin on Reducing Lupus Flares

Study Overview
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Brief Summary
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This is a multicenter, randomised, double-blind placebo controlled trial on the efficacy and safety of add-on metformin to conventional immunosuppressants in systemic lupus erythematosus (SLE). The purpose of this study is to evaluate: 1) the effect of metformin on reducing disease flares; 2) the influence of metformin on corticosteroid sparing effect; 3) the influence of metformin on body mass index (BMI); 4) the safety of metformin.

Official Title
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A Multicenter, Randomised, Double-blind Placebo Controlled Trial on the Efficacy and Safety of add-on Metformin to Conventional Immunosuppressants in Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness of the subject to participate in the study, proven by signing the informed consent; Systemic lupus erythematosus (SLE), as defined by meeting at least 4 of 11 classification criteria of American College of Rheumatology for the classification of systemic lupus erythematosus, either sequentially or coincidentally. The 4 criteria doesn't need to be present at the time of study enrollment; The course of SLE longer than1 year; and there is a clear record of disease flares in the past 1 year with prednisone more than 20mg/day; Patients with mild/moderate disease activity (score≤ 6 at screening on SLEDAI); no British Isles Lupus Assessment Group (BILAG) A or no more than one B; A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/ mycophenolate mofetil/ methotrexate/ ciclosporin/ leflunomide/ thalidomide) for at least 30 days. Exclusion Criteria: Patients who are unwilling to sign the inform consent; Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 times upper normal limits; creatinine clearance rate < 60ml/min; Patients who used cyclophosphamide 6-months before screening; used biological agents 12-months before screening; Previous exposure of metformin within 30 days before screening; or previous history of intolerant to metformin; Patients who diagnosed of diabetes mellitus; Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin<br>Eligible patients for clinical trial were randomized in a 1:1 ratio to metformin/placebo add-on. Subjects randomized to metformin will receive a target dose of 500 mg three times daily. Investigators were allowed to adjust the dose according to the patients' tolerance. | Drug: metformin<br>* 500 mg metformin three times daily<br>* Other names: Metformin Hydrochloride Tablets;|
| Placebo Comparator: placebo<br>Eligible patients for clinical trial were randomized in a 1:1 ratio to metformin/placebo add-on. Subjects randomized to placebo will receive a target dose of 500 mg three times daily. Investigators were allowed to adjust the dose according to the patients' tolerance. | Drug: placebo<br>* 500 mg placebo three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| numbers of participants who remained at risk of flares at each visit | the effect of metformin on reducing disease flares | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in prednisone dose from baseline at each visit | the influence of metformin on corticosteroid sparing effect | one year | 
| changes in BMI from baseline at each visit | the influence of metformin on BMI | one year | 
| number of participants with treatment-related adverse events | the safety of metformin | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin, systemic lupus erythematosus