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Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)

15 luglio 2013 aggiornato da: 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:

  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).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

221

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • North Carolina
      • Durham, North Carolina, Stati Uniti, 27715
        • Duke Medical Center / Duke Clinical Research Institute

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 10 anni a 21 anni (Bambino, Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: 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.
Altri nomi:
  • Lipitore
  • Atorvastatina Calcio
Comparatore placebo: 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.
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in Mean-Mean Common Carotid IMT (CIMT)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in Mean-Max CIMT
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in Total Cholesterol
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in HDL Cholesterol
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in LDL Cholesterol
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in Triglycerides
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in Lipoprotein A
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months
Change in Homocysteine
Lasso di tempo: Change from baseline to 36 months
Change from baseline to 36 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Laura Schanberg

Investigatori

  • Investigatore principale: Laura E. Schanberg, MD, Duke Medical Center

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2003

Completamento primario (Effettivo)

1 dicembre 2009

Completamento dello studio (Effettivo)

1 dicembre 2009

Date di iscrizione allo studio

Primo inviato

1 agosto 2003

Primo inviato che soddisfa i criteri di controllo qualità

1 agosto 2003

Primo Inserito (Stima)

4 agosto 2003

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

15 agosto 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 luglio 2013

Ultimo verificato

1 luglio 2013

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • Pro00006680
  • NIAMS-090
  • N01 AR022265

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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