Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)
Raktažodžiai
Santrauka
apibūdinimas
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.
Datos
Paskutinį kartą patikrinta: | 06/30/2013 |
Pirmasis pateikimas: | 07/31/2003 |
Numatytas registravimas pateiktas: | 07/31/2003 |
Pirmas paskelbtas: | 08/03/2003 |
Paskutinis atnaujinimas pateiktas: | 07/14/2013 |
Paskutinis atnaujinimas paskelbtas: | 08/14/2013 |
Pirmųjų rezultatų pateikimo data: | 02/10/2013 |
Pirmojo QC rezultatų pateikimo data: | 07/14/2013 |
Pirmųjų paskelbtų rezultatų data: | 08/14/2013 |
Faktinė studijų pradžios data: | 08/31/2003 |
Numatoma pirminio užbaigimo data: | 11/30/2009 |
Numatoma studijų užbaigimo data: | 11/30/2009 |
Būklė ar liga
Intervencija / gydymas
Drug: 1
Drug: 2
Fazė
Rankų grupės
Ranka | Intervencija / gydymas |
---|---|
Experimental: 1 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: 1 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. |
Placebo Comparator: 2 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: 2 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. |
Tinkamumo kriterijai
Amžius, tinkami studijuoti | 10 Years Į 10 Years |
Tinkamos studijoms lytys | All |
Priima sveikus savanorius | Taip |
Kriterijai | 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 |
Rezultatas
Pirminės rezultatų priemonės
1. Change in Mean-Mean Common Carotid IMT (CIMT) [Change from baseline to 36 months]
Antrinės rezultatų priemonės
1. Change in Mean-Max CIMT [Change from baseline to 36 months]
2. Change in Mean-Mean CIMT [Change from baseline to 36 months]
3. Change in Mean-Max Common CIMT [Change from baseline to 36 months]
4. Change in Mean-Max Internal CIMT [Change from baseline to 36 months]
5. Change in Mean-Mean Internal CIMT [Change from baseline to 36 months]
6. Change in Mean-Max Bifurcation CIMT [Change from baseline to 36 months]
7. Change in Mean-Mean Bifurcation CIMT [Change from baseline to 36 months]
8. Change in Mean-Max Far Wall CIMT [Change from baseline to 36 months]
9. Change in Mean-Mean Far Wall CIMT [Change from baseline to 36 months]
10. Change in Mean-Max Near Wall CIMT [Change from baseline to 36 months]
11. Change in Mean-Mean Near Wall CIMT [Change from baseline to 36 months]
12. Change in Natural Log of mg/L for hsCRP [Change from baseline to 36 months]
13. Change in Total Cholesterol [Change from baseline to 36 months]
14. Change in HDL Cholesterol [Change from baseline to 36 months]
15. Change in LDL Cholesterol [Change from baseline to 36 months]
16. Change in Triglycerides [Change from baseline to 36 months]
17. Change in Lipoprotein A [Change from baseline to 36 months]
18. Change in Homocysteine [Change from baseline to 36 months]