Treatment With Metformin in Chinese Children With Alport Syndrome

Study Overview
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Brief Summary
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This single-center, prospective, double-blind randomized placebo-controlled trial will evaluate the efficacy and safety of metformin in Chinese children with Alport syndrome who have received (and continue to receive)) ACEi/ARB.

Official Title
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Efficacy and Safety of Metformin in Alport Syndrome: A Randomized, Double-blind, Placebo-controlled Study in China

Conditions
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Alport Syndrome, Metformin

Intervention / Treatment
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* Drug: Metformin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) The diagnostic of Alport syndrome-hematuria with or without proteinuria meets one or more of the following 4 items: i) Immunofluorescence staining of the α5 (IV) chain of the glomerular basement membrane was abnormal; ii) electron microscopy of renal biopsy showed diffuse changes in the glomerular basement membrane; iii) There was one pathogenic variant in the COL4A5 gene or two pathogenic variants in the COL4A3/COL4A4 gene; iv) Family history of Alport syndrome. (2) Age is older than or equal to 10 years old. (3) The 24-hour urine protein quantification was greater than 150mg and the urine microalbumin-creatinine ratio was greater than 30 mg/g. (4) The estimated glomerular filtration rate (24-hour creatinine clearance) was greater than 45 mL/min/1.73m2. (5) Accept the maximum tolerated dose of renin-angiotensin-aldosterone system blockers (Blood pressure in the clinic was in the 50th percentile of the same age, same sex and same height but greater than 90/60mmHg, blood potassium was normal, and the increase of blood creatinine did not exceed 30%) for at least 3 months. Exclusion Criteria: (1) Vitamin B12 deficiency was uncorrected. (2) Treated with Furosemide, amiloride, and nifedipine. (3) Hypertension, chronic liver disease, chronic heart disease, and chronic kidney disease resulting from causes except Alport syndrome. (4) History of hyperlactatemia. (5) Allergy to metformin. (6) kidney transplant. (7) Poor compliance. (8) Type 1 diabetes.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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 |
| --- | --- |
| Active Comparator: Metformin intervention treatment group<br> | Drug: Metformin<br>* The participants will receive treatment of metformin (initial dose of 500 mg/day, within 2 weeks reaching the maximum tolerated dose [maximum: 1500 mg/day]).<br>|
| Placebo Comparator: The placebo treatment group<br> | Other: Placebo<br>* The participants will receive treatment of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of metformin for Alport syndrome | either decrease in proteinuria or steady eGFR from baseline. To assess the decrease in proteinuria or steady eGFR from baseline to month 12 or month 24 under metformin treatment compared to placebo | 24 months | 
| Safety of metformin for Alport syndrome | The occurrence of adverse events. Safety will be assessed by monitoring adverse drug events, physical examinations and clinical laboratory test through 24 months | 24 months |