Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)

Condition(s) targeted: Lupus Erythematosus, Systemic

Intervention: Atorvastatin (Drug); Placebo atorvastatin (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Official(s) and/or principal investigator(s):
Laura E. Schanberg, MD, Principal Investigator, Affiliation: Duke Medical Center

High cholesterol levels are common in people with Systemic Lupus Erythematosus (SLE). Atorvastatin is a drug that reduces cholesterol levels. This study will test whether atorvastatin can reduce cholesterol levels in children with SLE.

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Test the Safety and Efficacy of Lipitor (Atorvastatin) in Reducing the Progression of Carotid IMT in Early Childhood SLE

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Factorial Assignment, Efficacy Study

Primary outcome: Rate of progression of carotid IMT measured by carotid ultrasound

Secondary outcome:

Organ system damage as measured by modified SELENA-SLEDAI and SLICC-ACR Damage Index

Health-related quality of life as measured by PedsQL

Inflammatory mediators such as hs-CRP

Other IMT measures of progression rate

Serum lipid levels

Detailed description: Children and adolescents with SLE represent 15% of all SLE patients. Children with SLE suffer high morbidity that affects many organ systems, reduces their quality of life, and shortens their lifespan. As more children with SLE survive into adulthood, atherosclerotic cardiovascular disease has emerged as a major concern. SLE is a significant risk factor for myocardial infarction and death in young premenopausal women with SLE, even after controlling for traditional cardiovascular risk factors. Acceleration of atherogenesis in SLE most likely reflects SLE-associated vascular immune and inflammatory changes.

Although limited, the data on cardiovascular and lipid abnormalities in children with SLE implicate atherosclerosis as an important cause of long-term morbidity and mortality. The 3-hydroxy-3-methlglutaryl-coenzyme A (HMG CoA) reductase inhibitors, or statins, reduce mortality and morbidity from atherosclerosis in adults and have intrinsic anti-inflammatory and immune modulatory properties. These anti-inflammatory and immune modulatory activities may have particular benefit in the prevention and treatment of atherosclerosis in SLE. This trial will evaluate atorvastatin in children with SLE in the largest cohort of pediatric SLE patients ever studied prospectively.

Children in this study will be randomized to receive either atorvastatin or a placebo. All children will be followed for 3 years, during which they will have 15 study visits. Study visits will generally last 2 hours and will include medical interview, medication review and pill count, physical examination, and blood and urine tests. Cardiovascular-specific outcome measures will include assessments of high sensitivity CRP; fasting lipid profile; homocysteine level; apolipoprotein A, B1, and Lp(a); carotid intima media thickness (IMT); and tensor diffusion/MRI.

Minimum age: 10 Years. Maximum age: 21 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Meets American College of Rheumatology (ACR) revised diagnostic guidelines for SLE

- Weight of 25 kg (55 lbs) or more

- Outpatient

- Ability to complete self-report questionnaires in either English or Spanish

- Willingness to comply with recommended diet

- Acceptable methods of contraception

Exclusion Criteria:

- Drug-induced lupus

- Liver disease (ALT or aspartate aminotransferase greater than 2 X normal value)

- Myositis (CK greater than 3 X normal value)

- Inability to obtain adequate-quality IMT images

- Current use of oral or parenteral tacrolimus or cyclosporine

- Dialysis or serum creatinine reater than 2. 5 mg/dL

- Active nephrotic syndrome (urinary protein greater than 3 g/24 h and serum albumin

less than 2. 3 g/dl)

- Total cholesterol greater than 350 mg/dL

- Xanthoma

- Familial hypercholesterolemia

- Pregnant or breastfeeding

- Use of estrogen-containing contraceptives (e. g., Lo-Ovral)

- Unable to adhere to study regimen

- Life-threatening non-SLE illness that would interfere with ability to complete the

study

- Current drug or alcohol abuse

- Anticipated poor compliance

- Participation in another drug intervention study within 30 days of study enrollment

Duke Medical Center / Duke Clinical Research Institute, Durham, North Carolina 27715, United States

Starting date: September 2003
Ending date: November 2009
Last updated: January 7, 2008