Feasibility Study of Metformin Therapy in ADPKD

Phase 2

Completed

• Conditions: Polycystic Kidney, Autosomal Dominant
• Interventions: Drug: Placebo; Drug: Metformin

• Registration Number: NCT02903511
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2016-09-13
• Study First Submitted QC: 2016-09-15
• Study First Posted: 2016-09-16
• Study Start: 2016-11
• Primary Completion: 2020-08-17
• Study Completion: 2020-08-17
• Status Verified: 2021-08
• Results First Submitted: 2021-08-10
• Results First Submitted QC: 2021-08-10
• Last Update Submitted: 2021-08-10
• Results First Posted: 2021-09-05
• Last Update Posted: 2021-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive placebo 500 mg tablets, starting with 1 tab twice a day. The dose will be increased by 500 mg every 2 weeks up to 1000 mg by mouth twice a day, as tolerated, for 12 months.
Metformin	Metformin	Participants will receive metformin 500 mg tablets, starting with 1 tab twice a day. The dose will be increased by 500 mg every 2 weeks up to 1000 mg by mouth twice a day, as tolerated, for 12 months.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of Metformin	12 months	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

Secondary Outcome Measures

Name	Time	Method
Change in Total Kidney Volume	12 months	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.
Change in Kidney Function	12 months	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.
Rate of Serious Adverse Events (SAE)	12 months	Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms

Trial Locations

Locations (1)

University of Colorado Denver, Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States