Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
Status:
Not yet recruiting
Trial end date:
2022-01-30
Target enrollment:
Participant gender:
Summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal
disorder occurring in 1:400-1:1.000 live births and affects 4 to 6 million persons worldwide
and about 205.000 people in Europe (EU). This figure is equivalent to 4 in 10.000 people and
thus below the prevalence threshold of 5 in 10.000 used to designate a disease as rare in EU.
Renal cyst development and expansion in ADPKD involves both fluid secretion and abnormal
proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis
transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the
mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial
cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK).
Metformin, a drug widely used, is a pharmacological activator of AMPK. The investigators
found that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR
pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo
models of renal cystogenesis. In addition, metformin administration produces a significant
decrease in the cystic index in two mouse models of ADPKD. These results suggest a possible
role for AMPK activation in slowing renal cystogenesis as well as the potential for
therapeutic application of metformin in the context of ADPKD.
Thus this study aims to evaluate metformin efficacy in slowing renal cystogenesis in ADPKD as
compared to the actual gold standard (Tolvaptan).
Phase:
Phase 3
Details
Lead Sponsor:
Azienda Ospedaliero-Universitaria Consorziale Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari