Feasibility Study of Metformin Therapy in ADPKD

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 2

Conditions: Polycystic Kidney, Autosomal Dominant

Treatments: Drug: Placebo; Drug: Metformin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02903511

R21DK107969-01A1 (U.S. NIH Grant/Contract)

16-0802

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 patients

Sex: All

Ages: 30 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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56 participants in 2 patient groups, including a placebo group

Metformin

Experimental group

Description:

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.

Treatment:

Drug: Metformin

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo