Effect of Statin Therapy on Disease Progression in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• ClinicalTrials.gov Identifier: NCT00456365
• Recruitment Status: Completed
• First Posted: April 4, 2007
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Sponsor: University of Colorado, Denver
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

The purpose of this study is to determine whether the medication pravastatin will ameliorate renal and cardiovascular disease over a 3-year period in children and young adults with autosomal dominant polycystic kidney disease (ADPKD).

Condition or disease	Intervention/treatment	Phase
Polycystic Kidney, Autosomal Dominant	Drug: pravastatin; Drug: Placebo	Phase 3

Detailed Description:

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, affecting 1 in 400 to 1000 individuals and accounting for 4% of end-stage renal disease in the United States and 8-10% in Europe. The condition is characterized by progressive development of kidney cysts with kidney enlargement and associated loss of kidney function. High blood pressure and cardiovascular disease are common in patients with ADPKD. Although the condition is often thought to affect primarily adults, it is clear that the disease can be present in the fetus and young children.

This study was designed to determine if treatment with the medicine pravastatin can slow the progression of kidney and heart disease when initiated early in life in patients with ADPKD. The Investigators will assess differences between pravastatin and placebo study groups over the three-year study period with respect to: 1) total kidney volume as assessed by magnetic resonance imaging (MRI); 2) left ventricular mass index as assessed by MRI; 3) urinary albumin excretion; and 4) endothelial-dependent vasodilation as assessed by brachial ultrasound. A total of 110 subjects were enrolled in this research study. This study involved pediatric subjects because the Investigators believe that early intervention is critical if they are to decrease the morbidity and mortality associated with this condition. If pravastatin is shown to be effective in ameliorating progression of renal and cardiovascular disease in this study, routine management of people with this condition will be drastically altered.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Statin Therapy on Disease Progression in Autosomal Dominant Polycystic Kidney Disease
• Study Start Date: November 2006
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pravastatin; Pravastatin	Drug: pravastatin; Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)
Placebo Comparator: Placebo; Placebo	Drug: Placebo; Placebo daily

Outcome Measures

Primary Outcome Measures :

1. Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume [ Time Frame: 3 years ]
   Percent of participants demonstrating 20% or more increase in total kidney volume corrected for height, left ventricular mass index, or urinary albumin excretion over the three year study period

Secondary Outcome Measures :

1. Percentage Change in Total Kidney Volume Corrected for Height [ Time Frame: 3 years ]
2. Left Ventricular Mass Index [ Time Frame: 3 years ]
   left ventricular mass index in g/m^2 by MRI
3. Urinary Albumin Excretion [ Time Frame: 3 years ]

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 22 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 8-22 years
• Autosomal dominant polycystic kidney disease
• Normal kidney function

Exclusion Criteria:

• Abnormal kidney function
• Past allergic history to medications used in study
• Liver disease
• Muscle disease/dystrophy
• Pregnancy, planned pregnancy, or lactation within study period
• Inability to cooperate with or clinical contraindication for magnetic resonance imaging

Contacts and Locations

Locations

United States, Colorado

University of Colorado at Denver and Health Sciences Center

Denver, Colorado, United States, 80262

Sponsors and Collaborators

University of Colorado, Denver

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Melissa A Cadnapaphornchai, MD; University of Colorado, Denver
• Principal Investigator: Robert W Schrier, MD; University of Colorado, Denver

More Information

Additional Information:

PKD Foundation website 

Publications:

Schrier RW. Optimal care of autosomal dominant polycystic kidney disease patients. Nephrology (Carlton). 2006 Apr;11(2):124-30. Review.

Shamshirsaz AA, Reza Bekheirnia M, Kamgar M, Johnson AM, McFann K, Cadnapaphornchai M, Nobakhthaghighi N, Schrier RW. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int. 2005 Nov;68(5):2218-24. Erratum in: Kidney Int. 2005 Dec;68(6):2936. Shamshirsaz, Abdollah [corrected to Abdollah Shamshirsaz, Alireza]; Bekheirnia, Reza M [corrected to Reza Bekheirnia, Mir]; Haghighi, NN [corrected to Nobakhthaghighi, Niloofar].

Taylor M, Johnson AM, Tison M, Fain P, Schrier RW. Earlier diagnosis of autosomal dominant polycystic kidney disease: importance of family history and implications for cardiovascular and renal complications. Am J Kidney Dis. 2005 Sep;46(3):415-23.

Cadnapaphornchai MA, Fick-Brosnahan GM, Duley I, Johnson AM, Strain JD, DeGroff CG, Schrier RW. Design and baseline characteristics of participants in the study of antihypertensive therapy in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). Contemp Clin Trials. 2005 Apr;26(2):211-22.

Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis. 2002 Jun;39(6):1127-34.

Kelleher CL, McFann KK, Johnson AM, Schrier RW. Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens. 2004 Nov;17(11 Pt 1):1029-34.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00456365
• Other Study ID Numbers: 05-0704; 2R01DK058793 ( U.S. NIH Grant/Contract )
• First Posted: April 4, 2007
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:

Autosomal dominant polycystic kidney disease; Cystic kidney disease; High blood pressure; Statin

Additional relevant MeSH terms:

Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Disease Progression; Urologic Diseases; Disease Attributes; Pathologic Processes; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Kidney Diseases, Cystic; Abnormalities, Multiple; Ciliopathies; Genetic Diseases, Inborn; Pravastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors