Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)
15. července 2013 aktualizováno: Laura Schanberg
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
The purpose of this study is:
- 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.
- To assess the safety of intermediate-term (36 months) treatment of children and young adults with atorvastatin.
- To further characterize the course of SLE in children and young adults, by establishing a cohort of pediatric SLE patients to be followed prospectively.
- To establish a mechanism for conducting clinical trials in rare pediatric rheumatic diseases using the Children's Arthritis and Rheumatology Research Alliance (CARRA).
Přehled studie
Postavení
Dokončeno
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Intervenční
Zápis (Aktuální)
221
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
-
-
North Carolina
-
Durham, North Carolina, Spojené státy, 27715
- Duke Medical Center / Duke Clinical Research Institute
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
10 let až 21 let (Dítě, Dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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.
|
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.
Ostatní jména:
|
|
Komparátor placeba: 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.
|
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.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in Mean-Mean Common Carotid IMT (CIMT)
Časové okno: Change from baseline to 36 months
|
For the common carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right common near wall mean, right common far wall mean, left common near wall mean and left common far wall mean).
These summary variables were then averaged to estimate a single mean-mean common CIMT for each participant visit.
|
Change from baseline to 36 months
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in Mean-Max CIMT
Časové okno: Change from baseline to 36 months
|
For each side, segment and wall, the maximum CIMT over the 4 angles of interrogation was selected to produce 12 summary variables (right common near wall max, right common far wall max, right bifurcation near wall max, right bifurcation far wall max, right internal near wall max, right internal far wall max, left common near wall max, left common far wall max, left bifurcation near wall max, left bifurcation far wall max, left internal near wall max and left internal far wall max).
These 12 summary variables were then averaged to estimate a single mean-max CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Mean CIMT
Časové okno: Change from baseline to 36 months
|
For each side, segment and wall, mean CIMT values were averaged over the 4 angles of interrogation to produce 12 summary variables (right common near wall mean, right common far wall mean, right bifurcation near wall mean, right bifurcation far wall mean, right internal near wall mean, right internal far wall mean, left common near wall mean, left common far wall mean, left bifurcation near wall mean, left bifurcation far wall mean, left internal near wall mean and left internal far wall mean).
These 12 summary variables were then averaged to estimate a single mean-mean CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Max Common CIMT
Časové okno: Change from baseline to 36 months
|
For each side and wall of the common carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right common near wall max, right common far wall max, left common near wall max and left common far wall max).
These summary variables were then averaged to estimate a single mean-max common CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Max Internal CIMT
Časové okno: Change from baseline to 36 months
|
For each side and wall of the internal carotid arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right internal near wall max, right internal far wall max, left internal near wall max and left internal far wall max).
These summary variables were then averaged to estimate a single mean-max internal CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Mean Internal CIMT
Časové okno: Change from baseline to 36 months
|
For the internal carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right internal near wall mean, right internal far wall mean, left internal near wall mean and left internal far wall mean).
These summary variables were then averaged to estimate a single mean-mean internal CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Max Bifurcation CIMT
Časové okno: Change from baseline to 36 months
|
For each side and wall of the bifurcation arterial segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 4 summary variables (right bifurcation near wall max, right bifurcation far wall max, left bifurcation near wall max and left bifurcation far wall max).
These summary variables were then averaged to estimate a single mean-max bifurcation CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Mean Bifurcation CIMT
Časové okno: Change from baseline to 36 months
|
For the bifurcation arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right bifurcation near wall mean, right bifurcation far wall mean, left bifurcation near wall mean and left bifurcation far wall mean).
These summary variables were then averaged to estimate a single mean-mean bifurcation CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Max Far Wall CIMT
Časové okno: Change from baseline to 36 months
|
For the far wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common far wall max, right bifurcation far wall max, right internal far wall max, left common far wall max, left bifurcation far wall max, and left internal far wall max).
These 6 summary variables were then averaged to estimate a single mean-max far wall CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Mean Far Wall CIMT
Časové okno: Change from baseline to 36 months
|
For the far wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common far wall mean, right bifurcation far wall mean, right internal far wall mean, left common far wall mean, left bifurcation far wall mean and left internal far wall mean).
These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Max Near Wall CIMT
Časové okno: Change from baseline to 36 months
|
For the near wall measurements for each side and segment, the maximum CIMT over the 4 angles of interrogation was selected to produce 6 summary variables (right common near wall max, right bifurcation near wall max, right internal near wall max, left common near wall max, left bifurcation near wall max, and left internal near wall max).
These 6 summary variables were then averaged to estimate a single mean-max near wall CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Mean-Mean Near Wall CIMT
Časové okno: Change from baseline to 36 months
|
For the near wall measurements for each side and segment, mean CIMT values were averaged over the 4 angles of interrogation to produce 6 summary variables (right common near wall mean, right bifurcation near wall mean, right internal near wall mean, left common near wall mean, left bifurcation wall mean and left internal far wall mean).
These 6 summary variables were then averaged to estimate a single mean-mean far wall CIMT for each participant visit.
|
Change from baseline to 36 months
|
|
Change in Natural Log of mg/L for hsCRP
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in Total Cholesterol
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in HDL Cholesterol
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in LDL Cholesterol
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in Triglycerides
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in Lipoprotein A
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
|
|
Change in Homocysteine
Časové okno: Change from baseline to 36 months
|
Change from baseline to 36 months
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Laura E. Schanberg, MD, Duke Medical Center
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- Gurion R, Tangpricha V, Yow E, Schanberg LE, McComsey GA, Robinson AB; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Avascular necrosis in pediatric systemic lupus erythematosus: a brief report and review of the literature. Pediatr Rheumatol Online J. 2015 Apr 23;13:13. doi: 10.1186/s12969-015-0008-x.
- Robinson AB, Tangpricha V, Yow E, Gurion R, Schanberg LE, McComsey GA; APPLE Investigators. Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy. Lupus Sci Med. 2014 Sep 10;1(1):e000037. doi: 10.1136/lupus-2014-000037. eCollection 2014.
- Robinson AB, Tangpricha V, Yow E, Gurion R, McComsey GA, Schanberg LE; APPLE Investigators. Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy. Lupus Sci Med. 2014 Apr 30;1(1):e000011. doi: 10.1136/lupus-2014-000011. eCollection 2014.
- Ardoin SP, Schanberg LE, Sandborg CI, Barnhart HX, Evans GW, Yow E, Mieszkalski KL, Ilowite NT, Eberhard A, Imundo LF, Kimura Y, Levy D, von Scheven E, Silverman E, Bowyer SL, Punaro L, Singer NG, Sherry DD, McCurdy DK, Klein-Gitelman M, Wallace C, Silver RM, Wagner-Weiner L, Higgins GC, Brunner HI, Jung L, Soep JB, Reed AM, Thompson SD; APPLE investigators. Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. Ann Rheum Dis. 2014 Mar;73(3):557-66. doi: 10.1136/annrheumdis-2012-202315. Epub 2013 Feb 22.
- Schanberg LE, Sandborg C, Barnhart HX, Ardoin SP, Yow E, Evans GW, Mieszkalski KL, Ilowite NT, Eberhard A, Imundo LF, Kimura Y, von Scheven E, Silverman E, Bowyer SL, Punaro M, 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 AM, Provenzale J, Thompson SD; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Use of atorvastatin in systemic lupus erythematosus in children and adolescents. Arthritis Rheum. 2012 Jan;64(1):285-96. doi: 10.1002/art.30645.
- 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. doi: 10.1002/art.24469.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. září 2003
Primární dokončení (Aktuální)
1. prosince 2009
Dokončení studie (Aktuální)
1. prosince 2009
Termíny zápisu do studia
První předloženo
1. srpna 2003
První předloženo, které splnilo kritéria kontroly kvality
1. srpna 2003
První zveřejněno (Odhad)
4. srpna 2003
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
15. srpna 2013
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
15. července 2013
Naposledy ověřeno
1. července 2013
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Kardiovaskulární choroby
- Cévní onemocnění
- Onemocnění imunitního systému
- Arterioskleróza
- Arteriální okluzivní onemocnění
- Autoimunitní onemocnění
- Nemoci pojivové tkáně
- Lupus erythematodes, systémový
- Ateroskleróza
- Molekulární mechanismy farmakologického působení
- Inhibitory enzymů
- Antimetabolity
- Anticholesteremická činidla
- Hypolipidemická činidla
- Látky regulující lipidy
- Inhibitory hydroxymethylglutaryl-CoA reduktázy
- Atorvastatin
Další identifikační čísla studie
- Pro00006680
- NIAMS-090
- N01 AR022265
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .