By KRISTA CONGER
Lucile Packard Children’s Hospital researchers are collaborating with scientists at Duke University Medical Center to organize the first-ever multicenter clinical trial aimed at preventing heart disease in children with systemic lupus erythematosus.
The researchers will test whether atorvastatin — a medication that reduces cholesterol levels in adults and children — is safe and effective in preventing the hardening of the arteries, or atherosclerosis, that leads to premature heart attacks and strokes in children and young adults who have lupus.
"As we’re doing a better job at treating the primary symptoms of lupus, patients are living longer," said Christy Sandborg, MD, chief of pediatric rheumatology. "These young people develop premature atherosclerosis and may have strokes. We know that atherosclerosis starts in adolescence even in healthy people; the problem may be exacerbated in people with childhood onset of lupus." Some studies estimate that young, pre-menopausal women with lupus are 50 times more likely to have a heart attack than their peers without lupus.
Sandborg is one of two principal investigators for the $10 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a division of the National Institutes of Health. Laura Schanberg, MD, associate professor of pediatrics at Duke University Medical Center, is the other principal investigator.
Although scientists aren’t sure why lupus leads to heart disease, they suspect that the autoimmune disease causes inflammation and subsequent plaque formation in the blood vessel walls. If the plaque ruptures, the resulting blood clot may break free from the vessel and cause a heart attack or stroke.
The researchers speculate that atorvastatin, which is marketed under the trade name Lipitor, may reduce this risk by lowering the amounts of cholesterol likely to contribute to plaque formation.
"Atorvastatin was recently approved for use in children with very high cholesterol," said Sandborg, who is also an associate professor of pediatrics in the School of Medicine, "and nobody’s ever looked at it in kids with lupus. This is a completely new way of looking at this problem and may result in a new treatment for these children." The randomized, double-blind trial, called APPLE for Atherosclerosis Prevention in Pediatric Lupus Erythematosus, will follow 280 children between the ages of 10 and 19 for a period of three years.
Half of the patients will be treated with atorvastatin and half will receive a placebo. Atherosclerosis progression will be monitored non-invasively by regular ultrasounds of the carotid artery, which supplies blood to the brain. Thickening of the arterial wall is a reliable indicator of atherosclerosis.
Patients will be recruited from 20 centers across the United States and Canada. Packard Children’s Hospital is expecting to enroll about 20 patients over the course of the next year. Duke’s Clinical Research Institute will gather and process the data.
In addition to studying the effectiveness of atorvastatin in this study population, researchers hope the trial will lead to other insights about lupus. About 15 percent of lupus patients develop the disease in childhood, and their symptoms tend to be more severe than those of adult-onset patients. There are about 15,000 children in the United States with lupus.
"This will be the first trial ever done in pediatric lupus patients and the largest study ever done," said Sandborg. "We’ll be gathering a lot of information about lupus in general and what happens to kids with lupus: the course of renal disease, the effectiveness of various other treatments. It’s an opportunity to learn more about lupus in kids and adults."
For more information about the study, call 723-8295.
Stanford Report, November 19, 2003