The Effect of Metformin on Reducing Lupus Flares (Met Lupus)

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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: metformin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Ethics Committee of Renji Hospital, Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin; 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; 500 mg metformin three times daily; Other Names: Metformin Hydrochloride Tablets
Placebo Comparator: placebo; 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; 500 mg placebo three times daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RenJi Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2016
• Primary Completion (Actual): December 13, 2017
• Study Completion (Actual): December 7, 2018

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimate): April 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; metformin
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: SHDC12015902

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided