Polycystic Kidney, Autosomal Dominant
Conditions
Keywords
Autosomal dominant polycystic kidney disease, Cystic kidney disease, High blood pressure, Statin
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.
Interventions
DRUGpravastatin
Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)
DRUGPlacebo
Placebo daily
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 22 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Total Kidney Volume Corrected for Height | 3 years | — |
| Left Ventricular Mass Index | 3 years | left ventricular mass index in g/m\^2 by MRI |
| Urinary Albumin Excretion | 3 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pravastatin Pravastatin
pravastatin: Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years) | 56 |
| Placebo Placebo
Placebo: Placebo daily | 54 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | oncologic diagnosis | 1 | 1 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Pravastatin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 16 years STANDARD_DEVIATION 4 | 16 years STANDARD_DEVIATION 4 | 16 years STANDARD_DEVIATION 4 |
| LDL cholesterol | 84 mg/dL STANDARD_DEVIATION 23 | 90 mg/dL STANDARD_DEVIATION 21 | 86 mg/dL STANDARD_DEVIATION 22 |
| Left ventricular mass index | 55 g/m^2 STANDARD_DEVIATION 12 | 53 g/m^2 STANDARD_DEVIATION 10 | 54 g/m^2 STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 56 participants | 54 participants | 110 participants |
| Sex: Female, Male Female | 34 Participants | 34 Participants | 68 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 42 Participants |
| Total cholesterol | 145 mg/dL STANDARD_DEVIATION 30 | 151 mg/dL STANDARD_DEVIATION 27 | 148 mg/dL STANDARD_DEVIATION 29 |
| Total kidney volume corrected for height | 336 ml/m STANDARD_DEVIATION 187 | 315 ml/m STANDARD_DEVIATION 175 | 326 ml/m STANDARD_DEVIATION 181 |
| Urinary albumin excretion | 27 mcg/min STANDARD_DEVIATION 37 | 51 mcg/min STANDARD_DEVIATION 123 | 39 mcg/min STANDARD_DEVIATION 79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 56 | 0 / 54 |
| serious Total, serious adverse events | 0 / 56 | 0 / 54 |
Outcome results
Primary
Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume
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
Time frame: 3 years
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pravastatin | Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume | 69 percentage of participants |
| Placebo | Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume | 88 percentage of participants |
p-value: 0.03Chi-squared
Secondary
Left Ventricular Mass Index
left ventricular mass index in g/m\^2 by MRI
Time frame: 3 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Left Ventricular Mass Index | 60 g/m^2 | Standard Deviation 15 |
| Placebo | Left Ventricular Mass Index | 58 g/m^2 | Standard Deviation 13 |
p-value: 0.69ANOVA
Secondary
Percentage Change in Total Kidney Volume Corrected for Height
Time frame: 3 years
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Percentage Change in Total Kidney Volume Corrected for Height | 23 Percent change | Standard Deviation 3 |
| Placebo | Percentage Change in Total Kidney Volume Corrected for Height | 31 Percent change | Standard Deviation 3 |
p-value: 0.02ANCOVA
Secondary
Urinary Albumin Excretion
Time frame: 3 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Urinary Albumin Excretion | 29 mcg/min | Standard Deviation 39 |
| Placebo | Urinary Albumin Excretion | 49 mcg/min | Standard Deviation 99 |
p-value: 0.21ANCOVA