NCT02656017

Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 97 (actual)
• Sponsor: Kyongtae Ty Bae, M.D., Ph.D. · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This study will test to see if metformin is safe and if it is tolerated compared to placebo in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages of chronic kidney disease. We will also measure its effect on progression of kidney disease as reflected in the kidney size and the kidney function, along with its effect on kidney pain and quality of life.

Detailed description

There is growing evidence that metformin, a drug widely used for the treatment of type 2 diabetes and polycystic ovary syndrome, may serve as a novel therapy for individuals in the early stages of Autosomal Dominant Polycystic Kidney Disease ADPKD by activating the metabolic sensor AMP-activated protein kinase (AMPK). AMPK is activated under conditions of metabolic and other cellular stresses. Through its actions on downstream mediators, AMPK activation during low energy states decreases cellular energy consumption while stimulating energy generating pathways. It has been shown that AMPK phosphorylates and inhibits cystic fibrosis transmembrane conductance regulator (CFTR), thus suppressing epithelial fluid and electrolyte secretion. Similarly, AMPK phosphorylates the tuberin protein, leading to indirect inhibition of the mTOR pathway. Thus, AMPK inhibits both CFTR and mTOR, suggesting that targeted activation of this kinase by metformin may provide a therapeutic benefit in ADPKD. It has been shown that metformin treatment of kidney epithelial cells leads to stimulation of AMPK and subsequent inhibition of both mTOR and CFTR activity. It has also been shown that metformin slows cystogenesis in animal models of PKD, supporting the potential of this drug in ADPKD treatment.

Conditions

• Polycystic Kidney, Autosomal Dominant

Interventions

Type	Name	Description
DRUG	Metformin	Monitoring of tolerability and symptoms.
OTHER	Placebo	Monitoring of tolerability and symptoms.

Timeline

• Start date: 2016-06-27
• Primary completion: 2020-12-07
• Completion: 2020-12-07
• First posted: 2016-01-14
• Last updated: 2022-08-09
• Results posted: 2022-08-09

Locations

2 sites across 1 country: United States