Clinical trial NCT02903511: Feasibility Study of Metformin Therapy in ADPKD
Official title: Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polycystic Kidney, Autosomal Dominant
Keywords: Metformin
total kidney volume
glomerular filtration rate
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2016-09-16
Enrollment: 56
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to determine if treatment with metformin, a drug widely used for the treatment of diabetes type 2, is safe and well tolerated by individuals with Autosomal Dominant Polycystic Kidney Disease (ADPKD) who are not diabetic and who have slightly decreased kidney function. The study will also evaluate the effects of metformin on kidney growth and kidney function.

Detailed description: Patients with ADPKD are still in need for a well-tolerated treatment that can be used long-term to prevent cyst growth and kidney function decline. Metformin has a long track record of a low risk-to-benefit profile in patients with diabetes or at risk for diabetes. Metformin inhibits two key processes responsible for the growth of polycystic kidneys, i.e. fluid secretion and cell proliferation, as shown in cell cultures and animal models of ADPKD. Experiments in animal models of chronic kidney disease demonstrate that metformin administration prevents kidney fibrosis and preserves kidney function. Diabetic patients who are treated with metformin appear to develop less kidney failure and live longer than patients who are treated with other anti-diabetic medications. Therefore this drug is promising for people with ADPKD, with the potential to slow cyst enlargement and preserve kidney function.

Eligibility criteria: Inclusion Criteria:

* Autosomal Dominant Polycystic Kidney Disease and
* An estimated glomerular filtration (GFR) rate of 50-80 ml/min/1.73 m2;
* Subject is able to sign an Informed Consent

Exclusion Criteria:

* Diabetes mellitus,
* Active infection,
* Congestive heart failure,
* Liver disease,
* Alcohol or substance dependence,
* Cigarette smoking within the last 12 months;
* Females who are pregnant or breast feeding, or
* Are unwilling to use contraception;
* Are unable to undergo magnetic resonance imaging, or
* Have a contraindication to the use of metformin

Primary outcomes:
measure: Safety and Tolerability of Metformin
timeFrame: 12 months
Secondary outcomes:
measure: Change in Total Kidney Volume
timeFrame: 12 months
measure: Change in Kidney Function
timeFrame: 12 months
measure: Rate of Serious Adverse Events (SAE)
timeFrame: 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver, Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Godela M Brosnahan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2462-7. doi: 10.1073/pnas.1011498108. Epub 2011 Jan 24.
citation: Satriano J, Sharma K, Blantz RC, Deng A. Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease. Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F727-33. doi: 10.1152/ajprenal.00293.2013. Epub 2013 Jul 3.
citation: Hung AM, Roumie CL, Greevy RA, Liu X, Grijalva CG, Murff HJ, Griffin MR. Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control. Pharmacoepidemiol Drug Saf. 2013 Jun;22(6):623-31. doi: 10.1002/pds.3432.
citation: Brosnahan GM, Wang W, Gitomer B, Struemph T, George D, You Z, Nowak KL, Klawitter J, Chonchol MB. Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study. Am J Kidney Dis. 2022 Apr;79(4):518-526. doi: 10.1053/j.ajkd.2021.06.026. Epub 2021 Aug 12.