A Clinical Trial of Metformin to Decrease Glucocorticoids Side Effects in Patients With Autoimmune Uveitis

Study Overview
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Brief Summary
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This project is designed to evaluating the use of combination therapy of glucocorticoid and metformin to decrease glucocorticoid side effects in participants with autoimmune uveitis.This study also aims to evaluate the anti-inflammatory and immunosuppressive effects of combination therapy.

Detailed Description
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Approval of the study was obtained from the hospital's ethical committee. The study design and methodology followed the tenets of Declaration of Helsinki. All participants were provided with written informed consent and received a thorough explanation of the study design, aims, and the side effect of metformin. This is a multicenter, randomized, controlled clinical trial research. According to 1:1 ratio, all participants are randomly divided into two groups, the metformin group and placebo group. According to the fasting blood glucose (FBG), triglycerides (TG),total cholesterol (TC) and body mass index (BMI), the investigators compared experimental group with control group to evaluate whether the use of combination therapy of glucocorticoid and metformin decrease glucocorticoid side effects in participants with autoimmune uveitis. According to best corrected visual acuity (BCVA), anterior chamber and vitreous inflammation, fluorescence fundus angiography (FFA), electroretinogram (ERG) and so on, the investigators evaluate the anti-inflammatory and immunosuppressive effects of metformin in treatment of autoimmune uveitis.

Official Title
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Multicenter, Randomized, Controlled Clinical Trial Research Evaluating the Use of Combination Therapy of Glucocorticoids and Metformin to Decrease Glucocorticoids Side Effects in Patients With Autoimmune Uveitis

Conditions
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Uveitis, Metformin, Glucocorticoid

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Attending Tianjin Medical University Eye Hospital, ophthalmology department of Peking Union Medical College Hospital, ophthalmology department of Peking University First Hospital and Zhongshan Ophthalmic Center Sun Yat-sen University from January 2018 to January 2022. Chronic and non-infectious autoimmune uveitis with systemic glucocorticoids treatment (Initiation dosage ≥ 1 mg/kg/d or ≥ 50 mg/d). FBG < 6.1 mmol/L, HbAlc<6.O%, TC <6.2 mmol/L(240 mg／d1) and TG <2.3 mmol/L(200 mg／dl). All genders, age ≥ 18 years old. Ready for systemic glucocorticoids treatment. Willing to follow all study requirements and sign the informed consent. Without history of cancer and serious systemic diseases. Exclusion Criteria: Participate in other clinical trials within the preceding one years Planning ophthalmologic surgery over the next three months. With other sight-threatening diseases except cataract, such as glaucoma, diabetic retinopathy, retinal detachment, and so on. Taking or will take immunosuppressants which affecting glycometabolism and lipid metabolism except methotrexate,mycophenolate and azathioprine. Any known history of a serious infection (e.g., HIV, hepatitis, pneumonia, syphilis or tuberculosis). Any known history of diabetes mellitus, severe hepatic, renal or heart disease. Any known history of drug addiction, drug abuse and malignant tumor. Presence of a transplanted solid organ. Pregnant women and nursing mothers. Any known history of mental disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin group<br>Oral metformin 500 mg once daily for first week, 500 mg twice daily for next 23 weeks. The follow-up treatment according to the participants' condition. | Drug: Metformin<br>* The investigators assumed that the combination therapy of metformin and glucocorticoids can decrease glucocorticoids side effects and synergia the anti-inflammatory and immune inhibitory effect of glucocorticoids. So the investigators use metformin in the experimental group.<br>|
| Placebo Comparator: Placebo group<br>Oral placebo 500 mg once daily for first week, 500 mg twice daily for next 23 weeks. The follow-up treatment according to the participants' condition. | Drug: Placebo<br>* The investigators use placebo in the control group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of abnormal metabolic indexes | The assessments of abnormal metabolic indexes include any of these outcome measures: FBG≥6.1 mmol/L, TC≥6.2 mmol/L (240 mg/d1), TG≥2.3 mmol/L (200 mg/dl) or BMI increased 1 kg/m^2 than before in the process of follow-up twice in a row. | 24 weeks |