Feasibility Study of Metformin Therapy in ADPKD

Polycystic Kidney, Autosomal Dominant Clinical Trial

Official title:

Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02903511
• Other study ID #: 16-0802
• Secondary ID: R21DK107969-01A1
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: August 17, 2020

Study information

• Verified date: August 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 17, 2020
• Est. primary completion date: August 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Metformin
Monitoring of safety and tolerability
• Placebo
Monitoring of safety and tolerability

Locations

Country	Name	City	State
United States	University of Colorado Denver, Anschutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of Metformin	Percentage of participants who at the end of 12 months are still prescribed the full randomized dose of metformin or placebo, and the percentage of participants who are prescribed at least 50% of the randomized dose	12 months
Secondary	Change in Total Kidney Volume	Total kidney volume will be measured by MRI (magnetic resonance imaging) at baseline and at 12 months. Percentage change from baseline in height-adjusted total kidney volume is reported.	12 months
Secondary	Change in Kidney Function	Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine measurements at baseline and after 3, 6, 9 and 12 months. Change from baseline at 12 months is reported.	12 months
Secondary	Rate of Serious Adverse Events (SAE)	Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms	12 months