Statin Therapy in Patients With Early Stage ADPKD

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Autosomal Dominant Polycystic Kidney; ADPKD
• Intervention / Treatment: Drug: Placebo; Drug: Pravastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Inactive tablet
Active Comparator: Pravastatin; 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; Anti-inflammatory, anti-oxidative stress, and anti-proliferative therapy

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Vessel Stiffness	Blood vessel stiffness, as assessed by carotid-femoral pulse wave velocity, at baseline and after 2 years	Baseline, 2 years

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Michel Chonchol, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, Schrier RW. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014 May;9(5):889-96. doi: 10.2215/CJN.08350813. Epub 2014 Apr 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2017
• Primary Completion (Actual): March 25, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (Actual): September 6, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Statin; Pravastatin
• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin
• Other Study ID Numbers: 17-0678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No