Clinical trial NCT00456365: Effect of Statin Therapy on Disease Progression in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official title: Effect of Statin Therapy on Disease Progression in Autosomal Dominant Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycystic Kidney, Autosomal Dominant
Keywords: Autosomal dominant polycystic kidney disease
Cystic kidney disease
High blood pressure
Statin
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2007-04-04
Enrollment: 110
Sex: ALL
Minimum age (years): 8
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume
timeFrame: 3 years
Secondary outcomes:
measure: Percentage Change in Total Kidney Volume Corrected for Height
timeFrame: 3 years
measure: Left Ventricular Mass Index
timeFrame: 3 years
measure: Urinary Albumin Excretion
timeFrame: 3 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado at Denver and Health Sciences Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Melissa A Cadnapaphornchai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Robert W Schrier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schrier RW. Optimal care of autosomal dominant polycystic kidney disease patients. Nephrology (Carlton). 2006 Apr;11(2):124-30. doi: 10.1111/j.1440-1797.2006.00535.x.
citation: 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. doi: 10.1111/j.1523-1755.2005.00678.x.
citation: 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. doi: 10.1053/j.ajkd.2005.05.029.
citation: 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. doi: 10.1016/j.cct.2005.01.001.
citation: 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. doi: 10.1053/ajkd.2002.33379.
citation: 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. doi: 10.1016/j.amjhyper.2004.06.020.