Feasibility Study of Metformin Therapy in ADPKD

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Polycystic Kidney, Autosomal Dominant

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>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. | Drug: Metformin<br>* Monitoring of safety and tolerability<br>* Other names: Glumetza;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Monitoring of safety and tolerability<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, total kidney volume, glomerular filtration rate