Researchers at Washington University School of Medicine in St. Louis are seeking volunteers who are slightly overweight or who have elevated blood pressure. They want to see whether it’s possible to reduce the progression of atherosclerosis in healthy people by giving low doses of the malaria drug chloroquine.
The human study follows a mouse study that found chloroquine could blunt the progression of plaque buildup in mice that had a genetic predisposition to atherosclerosis.
“Vascular events such as heart attack and stroke are the biggest health risk facing Americans today,” says Janet B. McGill, M.D., associate professor of medicine in the Division of Endocrinology, Metabolism and Lipid Research. “Healthy adults with modest elevations in blood pressure or cholesterol or with an abundant waistline are often at higher-than-normal risk due to the silent buildup of atherosclerotic plaque in their arteries. That’s an indicator of higher risk for vascular events in the future.”
McGill is looking for healthy adults between 18 and 70 years of age with some of those risk factors to participate in an NIH-funded clinical trial. They’ll receive a low dose of the malaria drug chloroquine or an inactive placebo for one year. At the start of the study and again after drug therapy, McGill and her colleagues will conduct an ultrasound test on the carotid blood vessel and an MRI to examine the thickness of the vessels.
“In people at risk, we would expect to see a very slight thickening of these vessels,” says Clay F. Semenkovich, M.D., the Herbert S. Gasser Professor and chief of the Division of Endocrinology, Metabolism and Lipid Research. “We want to learn whether chloroquine can slow that thickening.”
Semenkovich and colleagues at St. Jude Hospital for Children in Memphis, Tenn., found that a small dose of chloroquine eased many metabolic symptoms in mice — reducing blood pressure, decreasing hardening and narrowing of the arteries and improving glucose tolerance. Those mice had been genetically engineered without a gene that makes an enzyme called ATM (ataxia telangiectasia mutated). Children without the gene develop a serious disorder called ataxia telangiectasia (AT). In addition to many other problems, children with AT develop an unusual type of diabetes.
Mice without ATM develop atherosclerosis, but when Semenkovich and his colleagues at St. Jude treated the mice with chloroquine, they no longer got atherosclerosis. It’s not clear if people who develop atherosclerosis also have deficiencies in ATM, but McGill says it appears to be worth a look.
“This is an early proof-of-concept study,” she explains. “If the concept works, we can then figure out the best doses of chloroquine and someday conduct a long-term study where we don’t just use ultrasounds to look at the thickness of blood vessels but actually follow people to see whether they have fewer heart attacks and strokes following chloroquine therapy.”
The study, called the Atheroma Reduction with Chloroquine in the Metabolic Syndrome (ARCH-MS) study, will screen healthy adults to find those with mildly elevated blood glucose, blood pressure or triglycerides. In addition to ultrasound and MRI tests, some blood tests will be performed, and those who complete the one-year study and two-year follow-up visit will be eligible for up to $1,000 in compensation. Tests and study-related medications are provided free of charge.
Patients will be monitored for signs of atherosclerosis and undergo blood tests and other exams to detect side effects from the medication.
For more information about the study, call McGill’s office at (314) 362-8681 or contact study coordinator Stacy Hurst at (314) 747-3294 or (shurst@im.wustl.edu).
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.