Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)
Condition: Lupus Erythematosus, Systemic
MeSH terms: Atherosclerosis; Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is:

        1. To assess the efficacy of a lipid-lowering agent (atorvastatin) on the development of
           atherosclerosis that predisposes children with SLE to cardiovascular events in
           adulthood.

        2. To assess the safety of intermediate-term (36 months) treatment of children and young
           adults with atorvastatin.

        3. To further characterize the course of SLE in children and young adults, by establishing
           a cohort of pediatric SLE patients to be followed prospectively.

        4. To establish a mechanism for conducting clinical trials in rare pediatric rheumatic
           diseases using the Children's Arthritis and Rheumatology Research Alliance (CARRA).
    

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.
    

Intervention name(s): Atorvastatin; Placebo atorvastatin
Intervention type(s): Drug; Drug
Intervention description(s): Participants weighing more 50 kg will receive 10 mg of atorvastatin po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.; Participants weighing more 50 kg will receive 10 mg of placebo po qd as a starting dose, which will be increased to 20 mg po qd at the Day 30 visit and continue through month 36. Participants weighing less than 50 kg will receive a maximum of 10 mg po qd for 36 months.
Other intervention name(s): Lipitor; Atorvastatin Calcium
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Pediatric lupus; Atherosclerosis; SLE; HMG CoA reductase inhibitor