Clinical trial NCT02741960: The Effect of Metformin on Reducing Lupus Flares
Official title: A Multicenter, Randomised, Double-blind Placebo Controlled Trial on the Efficacy and Safety of add-on Metformin to Conventional Immunosuppressants in Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus
Keywords: metformin
systemic lupus erythematosus
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2016-04-18
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: numbers of participants who remained at risk of flares at each visit
timeFrame: one year
Secondary outcomes:
measure: changes in prednisone dose from baseline at each visit
timeFrame: one year
measure: changes in BMI from baseline at each visit
timeFrame: one year
measure: number of participants with treatment-related adverse events
timeFrame: one year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ethics Committee of Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Shuang Ye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang H, Li T, Chen S, Gu Y, Ye S. Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin. Arthritis Rheumatol. 2015 Dec;67(12):3190-200. doi: 10.1002/art.39296.
citation: Sun F, Geng S, Wang H, Wang H, Liu Z, Wang X, Li T, Wan W, Lu L, Teng X, Morel L, Ye S. Effects of metformin on disease flares in patients with systemic lupus erythematosus: post hoc analyses from two randomised trials. Lupus Sci Med. 2020 Oct;7(1):e000429. doi: 10.1136/lupus-2020-000429.