Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)
2013年7月15日 更新者：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).
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
221
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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North Carolina
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Durham、North Carolina、アメリカ、27715
- Duke Medical Center / Duke Clinical Research Institute
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
10年～21年 (子、大人)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
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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.
他の名前：
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プラセボコンパレーター：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.
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Mean-Mean Common Carotid IMT (CIMT)
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Mean-Max CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Mean CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Max Common CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Max Internal CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Mean Internal CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Max Bifurcation CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Mean Bifurcation CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Max Far Wall CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Mean Far Wall CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Max Near Wall CIMT
時間枠：Change from baseline to 36 months
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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.
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Change from baseline to 36 months
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Change in Mean-Mean Near Wall CIMT
時間枠：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.
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Change from baseline to 36 months
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Change in Natural Log of mg/L for hsCRP
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in Total Cholesterol
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in HDL Cholesterol
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in LDL Cholesterol
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in Triglycerides
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in Lipoprotein A
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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Change in Homocysteine
時間枠：Change from baseline to 36 months
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Change from baseline to 36 months
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Laura E. Schanberg, MD、Duke Medical Center
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2003年9月1日
一次修了 (実際)
2009年12月1日
研究の完了 (実際)
2009年12月1日
試験登録日
最初に提出
2003年8月1日
QC基準を満たした最初の提出物
2003年8月1日
最初の投稿 (見積もり)
2003年8月4日
学習記録の更新
投稿された最後の更新 (見積もり)
2013年8月15日
QC基準を満たした最後の更新が送信されました
2013年7月15日
最終確認日
2013年7月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Pro00006680
- NIAMS-090
- N01 AR022265
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。