Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE)

NCT00065806 | Completed Phase 3 Results DMC

• 3 other identifiers: Pro00006680NIAMS-090N01AR022265
• Study Type: interventional
• Target: 221
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

1. 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. 2.To assess the safety of intermediate-term (36 months) treatment of children and young adults with atorvastatin.
3. 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. 4.To establish a mechanism for conducting clinical trials in rare pediatric rheumatic diseases using the Children's Arthritis and Rheumatology Research Alliance (CARRA).

Conditions

Lupus Erythematosus, Systemic

Keywords

Pediatric lupus; Atherosclerosis; SLE; HMG CoA reductase inhibitor

Outcome Measures

Primary Outcomes (1)

• Change in Mean-Mean Common Carotid IMT (CIMT)

  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

Secondary Outcomes (18)

• Change in Mean-Max CIMT

  Change from baseline to 36 months

• Change in Mean-Mean CIMT

  Change from baseline to 36 months

• Change in Mean-Max Common CIMT

  Change from baseline to 36 months

• Change in Mean-Max Internal CIMT

  Change from baseline to 36 months

• Change in Mean-Mean Internal CIMT

  Change from baseline to 36 months

Study Arms (2)

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

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

Interventions

Atorvastatin DRUG

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.

Also known as: Lipitor, Atorvastatin Calcium

1

Placebo atorvastatin DRUG

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.

2

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Laura Schanberg: lead

Study Sites (1)

Duke Medical Center / Duke Clinical Research Institute

Durham, North Carolina, 27715, United States

Location

Related Publications (6)

• 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.

  PMID: 25902709 DERIVED

• 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.

  PMID: 25396067 DERIVED

• 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.

  PMID: 25396060 DERIVED

• 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.

  PMID: 23436914 DERIVED

• 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.

  PMID: 22031171 DERIVED

• 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.

  PMID: 19404953 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Atherosclerosis

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Laura Schanberg, MD
• Organization: Duke University Medical Center

laura.schanberg@duke.edu

919-684-6575

Study Officials

• Laura E. Schanberg, MD

  Duke Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Director, Professor

Study Record Dates

• First Submitted: August 1, 2003
• First Posted: August 4, 2003
• Study Start: September 1, 2003
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 15, 2013
• Results First Posted: August 15, 2013

Record last verified: 2013-07

Locations

US (1)