Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome

OBJECTIVES:

I. Determine the effect of atorvastatin on the plasma levels of lipids, Lp(a), and apoproteins for treating hyperlipidemia in children with nephrotic syndrome in whom proteinuria and hyperlipidemia persist after other appropriate measures to treat their primary disease have been exhausted.

II. Determine the safety and tolerability of atorvastatin in these patients.

III. Provide preliminary data for a future investigation into the potential effect that lowering cholesterol levels may have on the rate of progression of renal insufficiency in such patients.

Study Overview

• Status: Terminated
• Conditions: Hyperlipidemia; Nephrotic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Atorvastatin

Detailed Description

PROTOCOL OUTLINE:

This is a randomized, double blind, placebo controlled, multicenter study.

After 3 months of low cholesterol diet, patients are randomized to receive atorvastatin tablets daily (arm I) or placebo tablets daily (arm II) for 3 months. Arm I patients receive increasing doses of atorvastatin every 4 weeks until individual maximum tolerated doses (MTDs) are determined.

After 3 months of treatment, all patients are given atorvastatin in a 6-9 month open label extended evaluation. Arm I patients receive atorvastatin for an additional 6 months and arm II patients receive atorvastatin for 9 months with increasing doses of atorvastatin every 4 weeks for the first 3 months until MTDs are determined.

Patients are followed every 6-8 weeks for one year.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Chronic hyperlipidemia with treatment-resistant nephrotic syndrome; Must have received at least 2 months of therapy with steroids on a daily or alternate basis

Primary nephropathy described as minimal change nephrotic syndrome, mesangioproliferative glomerulonephritis, IgM neuropathy, and focal segmental glomerulosclerosis

Glomerular filtration rate at least 30 mL/min

LDL cholesterol at least 160 mg/dL

--Prior/Concurrent Therapy--

No concurrent medications affecting or interacting with lipids or atorvastatin, with the exception of angiotensin converting enzyme inhibitors at discretion of referring physician, including: lipid-lowering medications, beta blockers, thiazides, fish oils, cyclosporine, Cytoxan, azathioprine, chlorambucil, and erythromycin

Concurrent prednisone and other corticosteroids allowed on a continual basis at a dose of no greater than 1 mg/kg every other day (maximum dose, no greater than 40 mg every other day); Concurrent acute courses of steroids no greater than 1 week for other unrelated conditions (e.g., asthma) also allowed

--Patient Characteristics--

Hepatic: ALT or AST less than 2 times normal

Renal: See Disease Characteristics; Creatine phosphokinase less than 3 times normal

Other: No history of familial hypercholesterolemia; No systemic disease such as systemic lupus, Schoenlein-Henoch purpura, Hodgkin's disease, polyarteritis nodosum, sickle cell disease, or HIV; Not pregnant; Effective contraception required of all adolescent patients

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	Drug: Placebo
Experimental: Atorvastatin	Drug: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in plasma lipid levels	One year

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Southwest Pediatric Nephrology Study Group
• Investigators: Study Chair: Ronald Hogg, Southwest Pediatric Nephrology Study Group

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 1998
• Primary Completion (Actual): December 1, 1999
• Study Completion (Actual): December 1, 1999

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Actual): September 15, 2017
• Last Update Submitted That Met QC Criteria: September 14, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: rare disease; cardiovascular and respiratory diseases; hyperlipidemia; renal and genitourinary disorders; nephrotic syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Disease; Lipid Metabolism Disorders; Dyslipidemias; Syndrome; Hyperlipidemias; Nephrotic Syndrome; Nephrosis; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 199/13924; R21DK053611 (U.S. NIH Grant/Contract); PD-981-183 (Other Identifier: Southwest Pediatric Nephrology Study Group); SPNSG-97.024 (Other Identifier: Southwest Pediatric Nephrology Study Group)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No