Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) - Full Text View

Sponsor:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00065806

Purpose

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.

Condition	Intervention	Phase
Lupus Erythematosus, Systemic	Drug: Atorvastatin Drug: Placebo atorvastatin	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Lupus

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:

Rate of progression of carotid IMT measured by carotid ultrasound [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Organ system damage as measured by modified SELENA-SLEDAI and SLICC-ACR Damage Index [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Health-related quality of life as measured by PedsQL [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Inflammatory mediators such as hs-CRP [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Other IMT measures of progression rate [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Serum lipid levels [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment:	221
Study Start Date:	September 2003
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.	Drug: Atorvastatin 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.
2: Placebo Comparator Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.	Drug: Placebo atorvastatin 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.

Arms

Assigned Interventions

1: Experimental

Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.

Drug: Atorvastatin

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.

2: Placebo Comparator

Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.

Drug: Placebo atorvastatin

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.

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.

Eligibility

Ages Eligible for Study:	10 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00065806

Locations

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

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

Principal Investigator:

Laura E. Schanberg, MD

Duke Medical Center

More Information

No publications provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Levy DM, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy D, Klein-Gitelman M, Wallace C, Silver R, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed A; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. Arthritis Rheum. 2009 May;60(5):1496-507.

Responsible Party:	Duke Clinical Research Institute ( Laura Schanberg, MD )
Study ID Numbers:	N01 AR022265, NIAMS-090
Study First Received:	August 1, 2003
Last Updated:	May 13, 2009
ClinicalTrials.gov Identifier:	NCT00065806 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Pediatric lupus
Atherosclerosis
SLE
HMG CoA reductase inhibitor

Additional relevant MeSH terms:

Antimetabolites
Atherosclerosis
Arterial Occlusive Diseases
Autoimmune Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors

Arteriosclerosis
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Lupus Erythematosus, Systemic
Therapeutic Uses
Connective Tissue Diseases
Cardiovascular Diseases
Atorvastatin

ClinicalTrials.gov processed this record on November 09, 2009