AMPK-activation by Metformin in FSGS: AMP-FSGS

Description

The primary objective of this study is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS).Focal Segmental glomerulosclerosis (FSGS) is currently the most common primary glomerular disease that progresses to ESKD in the US. FSGS is typified by significant proteinuria, and by disorganization of the actin cytoskeleton of highly specialized epithelial cells which support the glomerular capillary loop called podocytes. Podocytes are characterized by foot processes, whose disorganization with injury is visualized on electron microscopy as foot process effacement (FPE). Podocytes are also incapable of self-renewal, and podocyte loss over \~40% per glomerulus leads to proteinuria, the nephrotic syndrome (NS) and FSGS. Such critical podocyte loss alone is sufficient for progressive CKD and ESKD. Currently, the reported rate o

Trial Eligibility

Inclusion Criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, aged greater than or equal to 18 years, but \</= 80 years age at the time of signing the informed consent 4. Biopsy-confirmed primary FSGS as defined by expert renal pathology at either institutions. For homogeneity of diagnoses, demonstrable segmental or global sclerosis lesions (\>/=1 glomerulus) with diffuse podocyte foot process effacement by electron microscopy (\>/+ 50% of examined glomerular tufts). 5. Therapeutic plan by treating physician for immunomodulatory treatment using Glucocorticoids. 6. Ability to take oral medication and be willing to adhere to the MF or Placebo regimen 7. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of VPA administration. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. Exclusion Criteria: 1. Liver disease: confirmed cirrhosis liver (any stage), acute hepatitis (\> 2 fold increase in liver enzymes, any coagulopathy, hyperbilirubinemia, ascites or encephalopathy) 2. estimated GFR \< 32 ml/min 3. Diabetes Mellitus diagnosis at the time of biopsy or need for oral hypoglycemic agents/Insulin, or taking Metformin for other indications 4. Treatment with another investigational drug or other intervention within 3 months 5. Current pregnancy or desire to become pregnant during the study period 6. Unwilling to use two forms of birth control (for women of childbearing age) 7. Under hospice care 8. Confirmed Dementia diagnoses in EMR problem list 9. Incarceration 10. Homelessness 11. Inability to consent 12. Currently enrolled in (or completed within the past 30 days) a study of an investigational drug or device. 13. Life expectancy of less than 6 months as determined by the clinical judgement of the patient's primary physician 14. Allergy or sensitivity to Metformin 15. Platelet count \< 100,000/µL; INR \> 1.5; Bleeding diathesis or blood thinner use contraindicating biopsy. 16. Simultaneous use of Carbonic anhydrase inhibitor agents 17. Use of systemic immunosuppressive medication for non-renal indications.

Study Info

Interventions

Locations Recruiting

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