The Effect of Metformin on Reducing Lupus Flares

NCT02741960 | Completed Phase 4 DMC

• 1 other identifier: SHDC12015902
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Lupus Erythematosus

Keywords

metformin; systemic lupus erythematosus

Outcome Measures

Primary Outcomes (1)

• numbers of participants who remained at risk of flares at each visit

  the effect of metformin on reducing disease flares

  one year

Secondary Outcomes (3)

• changes in prednisone dose from baseline at each visit

  one year

• changes in BMI from baseline at each visit

  one year

• number of participants with treatment-related adverse events

  one year

Study Arms (2)

metformin

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Interventions

metformin DRUG

500 mg metformin three times daily

Also known as: Metformin Hydrochloride Tablets

metformin

placebo DRUG

500 mg placebo three times daily

placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ethics Committee of Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200000, China

Location

Related Publications (3)

• 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.

  PMID: 26245802 BACKGROUND

• Sun F, Wang HJ, Liu Z, Geng S, Wang HT, Wang X, Li T, Morel L, Wan W, Lu L, Teng X, Ye S. Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2020 Apr;2(4):e210-e216. doi: 10.1016/S2665-9913(20)30004-7. Epub 2020 Feb 24.

  PMID: 38268156 DERIVED

• 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.

  PMID: 33093216 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Metformin

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Shuang Ye, MD

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director, Dept. Rheumatology, Renji Hospital South Campus

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 18, 2016
• Study Start: May 24, 2016
• Primary Completion: December 13, 2017
• Study Completion: December 7, 2018
• Last Updated: September 17, 2019

Record last verified: 2019-09

Locations

CN (1)