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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT00456365
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 110
• Location: 1
• Arms: 2
• Duration (Months): 71
• Patients Per Site Per Month: 1.5

Study Details

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
• 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: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 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 [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 [3 years]

2. Left Ventricular Mass Index [3 years]

   left ventricular mass index in g/m^2 by MRI

3. Urinary Albumin Excretion [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 22 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• PKD Foundation website

Publications

• 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.
• 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.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00456365
• Other Study ID Numbers: 05-0704; 2R01DK058793
• First Posted: Apr 4, 2007
• Last Update Posted: Mar 9, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Pravastatin

Study Results

Participant Flow

Arm/Group Title	Pravastatin	Placebo
Arm/Group Description	Pravastatin pravastatin: Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo Placebo: Placebo daily
Period Title: Overall Study
STARTED	56	54
COMPLETED	49	42
NOT COMPLETED	7	12

Baseline Characteristics

Arm/Group Title	Pravastatin	Placebo	Total
Arm/Group Description	Pravastatin pravastatin: Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo Placebo: Placebo daily	Total of all reporting groups
Overall Participants	56	54	110
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16 (4)	16 (4)	16 (4)
Sex: Female, Male (Count of Participants)
Female	34 60.7%	34 63%	68 61.8%
Male	22 39.3%	20 37%	42 38.2%
Region of Enrollment (participants) [Number]
United States	56 100%	54 100%	110 100%
Total kidney volume corrected for height (ml/m) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/m]	336 (187)	315 (175)	326 (181)
Urinary albumin excretion (mcg/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mcg/min]	27 (37)	51 (123)	39 (79)
Left ventricular mass index (g/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/m^2]	55 (12)	53 (10)	54 (11)
Total cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	145 (30)	151 (27)	148 (29)
LDL cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	84 (23)	90 (21)	86 (22)

Outcome Measures

1. Primary Outcome

Title	Percent of Participants Demonstrating 20% or More Increase in Total Kidney Volume
Description	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

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Pravastatin	Placebo
Arm/Group Description	Pravastatin pravastatin: Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo Placebo: Placebo daily
Measure Participants	49	42
Number [percentage of participants]	69 123.2%	88 163%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Percentage Change in Total Kidney Volume Corrected for Height
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Pravastatin	Placebo
Arm/Group Description	Pravastatin pravastatin: Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo Placebo: Placebo daily
Measure Participants	49	42
Mean (Standard Deviation) [Percent change]	23 (3)	31 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Left Ventricular Mass Index
Description	left ventricular mass index in g/m^2 by MRI
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pravastatin	Placebo
Arm/Group Description	Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo daily
Measure Participants	49	42
Mean (Standard Deviation) [g/m^2]	60 (15)	58 (13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Urinary Albumin Excretion
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pravastatin	Placebo
Arm/Group Description	Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)	Placebo daily
Measure Participants	49	42
Mean (Standard Deviation) [mcg/min]	29 (39)	49 (99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Pravastatin		Placebo
Arm/Group Description	Pravastatin 20 mg daily (subject age 8-12 years) or 40 mg daily (subject age 13-21 years)		Placebo daily
All Cause Mortality
	Pravastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pravastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Pravastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/54 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.