Statin Therapy in Patients With Early Stage ADPKD

Study Overview
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Brief Summary
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This study plans to learn if pravastatin is helpful in slowing down the progression of kidney disease in adults with autosomal dominant polycystic kidney disease (ADPKD). Pravastatin has been approved by the Food and Drug Administration (FDA) for adults for treatment of hyperlipidemia (high cholesterol levels). The investigators are using pravastatin in this study as an investigational drug for treatment of ADPKD.

Detailed Description
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This is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy and benefits of pravastatin therapy in adults with ADPKD by evaluating 1) kidney volume as measured by kidney magnetic resonance imaging (MRI); 2) renal blood flow as measured by kidney magnetic resonance angiography (MRA); 3) kidney function as assessed by Glofil-125; 4) plasma and urine protein markers that will allow a better understanding of how pravastatin works in ADPKD; and 5) blood vessel stiffness as measured by carotid-femoral pulse wave velocity. These parameters will be measured at baseline and after 2 years of pravastatin or placebo treatment in 150 patients with ADPKD.

Official Title
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Statin Therapy in Patients With Early Stage ADPKD

Conditions
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ADPKD, Autosomal Dominant Polycystic Kidney

Intervention / Treatment
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* Drug: Pravastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ADPKD Total kidney volume >500 mL Estimated glomerular filtration rate (GFR) ≥60 mL/min/1.73m^2 Controlled blood pressure <140/80 mmHg Exclusion Criteria: Uncontrolled hypertension Diabetes mellitus Renal disease, renal cancer, single kidney, recent renal surgery, or acute kidney injury Unstable angina Coronary artery disease Prior ischemic stroke Other clinical indication for a statin History of hospitalizations within the last 3 months Hepatic impairment or liver function abnormalities Secondary hypercholesterolemia or hypocholesterolemia Use of tolvaptan, gemfibrozil, other fibrates, niacin, clarithromycin, or cyclosporine Hypersensitivity to statins Immunosuppressive therapy within the last year Clinical contraindication for an MRI (i.e. implants, pacemaker, claustrophobia) Hypersensitivity to iodine Pregnant or breast feeding Current tobacco use Alcohol abuse or dependence

Ages Eligible for Study
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Minimum Age: 25 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
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel study design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive inactive 40 mg tablets of placebo everyday for 6 weeks. If well tolerated, participants will continue taking inactive 40 mg dose of placebo everyday for 2 years. | Drug: Placebo<br>* Inactive tablet<br>|
| Active Comparator: Pravastatin<br>Participants will receive 40 mg tablets of pravastatin everyday for 6 weeks. If well tolerated, participants will continue taking 40 mg dose of pravastatin everyday for 2 years. | Drug: Pravastatin<br>* Anti-inflammatory, anti-oxidative stress, and anti-proliferative therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Kidney Volume | Total kidney volume as assessed by renal MRI, at baseline and after 2 years of treatment | Baseline, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Renal Blood Flow | Renal blood flow, as assessed by renal MRA, at baseline and after 2 years of treatment | Baseline, 2 years | 
| Change in Kidney Function | Glomerular filtration rate (GFR), as assessed by Glofil-125, at baseline and after 2 years of treatment | Baseline, 2 years | 
| Change in Circulating Inflammatory Markers | Plasma levels of inflammatory cytokines and growth factors at baseline and after 2 years of treatment | Baseline, 2 years | 
| Change in Circulating Markers of Oxidative Stress | Plasma levels of oxidative stress markers at baseline and after 2 years of treatment | Baseline, 2 years | 
| Change in Urinary Epithelial Cells | Urinary epithelial cell protein expression, as assessed by immunofluorescence, at baseline and after 2 years of treatment | Baseline, 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pravastatin, Statin