Treatment With Metformin in Chinese Children With Alport Syndrome

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metformin; Alport Syndrome
• Intervention / Treatment: Drug: Metformin; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Active Comparator: Metformin intervention treatment group	Drug: Metformin; 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]).
Placebo Comparator: The placebo treatment group	Other: Placebo; The participants will receive treatment of placebo.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 3, 2023
• Primary Completion (Anticipated): January 31, 2025
• Study Completion (Anticipated): April 20, 2025

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Actual): December 19, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Connective Tissue Diseases; Nephritis; Collagen Diseases; Syndrome; Nephritis, Hereditary; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MCCAS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No