Atorvastatin to Prevent Avascular Necrosis of Bone in Steroid Treated Exacerbated Systemic Lupus Erythematosus

AVN Prevention With Lipitor in Lupus Erythematosus APLLE Trial

This study uses the cholesterol lowering drug atorvastatin, also known as lipitor, to show reduction of avascular necrosis in steroid treated lupus patients. Avascular necrosis is a disease resulting from the loss of blood supply to the bones which can cause the bone to collapse. The collapse of bone may require a surgical replacement of the joint and can be disabling for life. Avascular necrosis is presently not preventable but research has shown that lipid lowering drugs such as lipitor can reduce or prevent avascular necrosis in animals. We therefore hypothesize that lipitor will reduce the incidence of avascular necrosis in lupus patients taking high dose steroids.

Study Overview

• Status: Terminated
• Conditions: Avascular Necrosis
• Intervention / Treatment: Drug: Atorvastatin; Procedure: MRI, Venipuncture; Drug: Placebo

Detailed Description

If you have started on prednisone 30mg or greater and expect to be on it for greater than two weeks you may be a candidate for the study. Also, you would need to be enrolled in the study within three days of starting prednisone. If you are eligible you will receive lipitor 40mg per day or pills which look exactly like lipitor but do not contain any medication (called placebo). During the time of the study, you will not know if you are taking lipitor or the placebo. The period of time that you will receive lipitor or placebo is 9 months and you must be willing to return for 5 follow up visits during this time which include blood tests, physical exams and 3 MRI studies of the hips, knees and ankles.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10003
      • The New York University Hospital For Joint Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All individuals must fulfill 4 of the revised criteria of the American College of Rheumatology for SLE
• Patient started on corticosteroids at a dose of at least .5mg/kg for an interval greater than two weeks
• To be able to come for all follow-up visits for nine months
• No contraindications to undergoing MRI
• Age 18-75 years

Exclusion Criteria:

• Evidence of liver disease, not secondary to active lupus, or liver enzyme greater than 2x normal
• Elevated CPK at baseline
• Pregnancy or Lactating
• Allergy to a statin
• Current or recent use of a statin within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; Atorvastatin 40mg	Drug: Atorvastatin; Atorvastatin 40mg vs placebo 40mg daily; Other Names: Atorvasatatin 40mg vs Placebo; Procedure: MRI, Venipuncture; MRIs done baseline, four and nine months; Other Names: MRI at baseline, 4 months and 9 months
Placebo Comparator: Placebo; Tablets identical to atorvastatin 40mg	Procedure: MRI, Venipuncture; MRIs done baseline, four and nine months; Other Names: MRI at baseline, 4 months and 9 months; Drug: Placebo; Tablets identical to atorvastatin 40mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With AVN After 9 Months	9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With AVN After 4 Months	4 months
To Determine if Atorvastatin is Effective in Lowering Serum Lipid Levels Chol, TG, HDL, & LDL in SLE Patients	6 years
To Determine if Atorvastatin Has an Anti-inflammatory Effect in Active SLE That Reduces Biological Markers of the Inflammatory Process (ESR, Hs-CRP) and Reduces Disease Activity Assessed by Serology (C3, C4, Anti-dsDNA) or Clinical Instrument (SLEDAI)	6 years

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Howard M Belmont, M.D., The New York University Hospital For Joint Diseases

Publications and helpful links

General Publications

• Belmont HM, Lydon E. Avascular necrosis prevention with lipitor in lupus erythematosus. Lupus. 2005;14(10):869-70. doi: 10.1191/0961203305lu2189xx. No abstract available.

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: December 18, 2006
• First Submitted That Met QC Criteria: December 18, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Actual): November 23, 2018
• Last Update Submitted That Met QC Criteria: October 23, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: SLE; Lipitor; Avascular Necrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Bone Diseases; Necrosis; Osteonecrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: H-8795

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No