The largest study ever conducted in patients with Huntington's disease is beginning at 22 medical centers around the United States and Canada. The four-year trial, the first multi-center clinical trial for Huntington's to be sponsored by the National Institutes of Health, will be based at the University of Rochester.
Physicians conducting the $6.5-million study, funded by the National Institute of Neurological Disorders and Stroke (NINDS), will test two treatments for their ability to prevent deterioration in 340 patients with Huntington's disease: the experimental drug Remacemide, made by Astra Merck, and the nutritional supplement Coenzyme Q10 (CoQ10). The trial is called CARE-HD (Coenzyme Q10 and Remacemide: Evaluation in Huntington's Disease).
Huntington's is an inherited disorder caused by a genetic mutation on the fourth chromosome that affects 15,000 to 30,000 people in the U.S. The mutation results in the death of vital nerve cells in a region of the brain known as the striatum that controls motor movements. Symptoms usually begin to appear in early to mid-adulthood and include involuntary movements of the limbs or facial muscles, problems with coordination, cognitive difficulties, and depression. The disease progresses and usually leads to death over 15 or 20 years.
While certain drugs are now used to treat some of the symptoms of Huntington's, there is no drug treatment for the underlying disease.
Previous short-term studies have shown that both medications being tested are safe. Remacemide blocks a neurotransmitter in the brain suspected of contributing to the death of brain cells in Huntington's disease. CoQ10 is a nutritional supplement that plays a role in the function of mitochondria, the energy factories of human cells. CoQ10 is also an anti-oxidant, helping soak up compounds known as free radicals that do damage to DNA and other proteins in our body. Research shows that both damage from free radicals and a reduced supply of cellular energy may contribute to Huntington's.
In the current investigation, 340 patients will be studied over a period of 30 months. Some patients will receive one of the two medications, some will receive both, and some will receive only a placebo. In what is known as a randomized double-blind study, even the doctors won't know which patients have received which, if any, treatment, until the study code is broken in four years. While doctors don't expect to reverse or eliminate patients' symptoms, they hope to demonstrate whether the interventions slow the worsening of the disease.
The study was designed and is being conducted by the Huntington Study Group, which is supported by the Huntington's Disease Society of America in New York; Foundation for the Care and Cure of Huntington's Disease in Islamorada, Fla.; the Huntington Society of Canada in Cambridge, Canada; and the Hereditary Disease Foundation in Santa Monica, Calif.
The study's principal investigator is Karl Kieburtz, M.D., associate professor of neurology at the University of Rochester. Walter Koroshetz, M.D., associate professor of neurology at Massachusetts General Hospital in Boston, is the co-principal investigator.
At selected hospitals throughout North America, patients with Huntington's who consent to the study will be treated and evaluated regularly for any change in their symptoms. At Massachusetts General Hospital physicians will use magnetic resonance spectroscopy on some participants to look for drug- induced improvement in the level of certain brain chemicals.
At the University of Rochester, physicians will see patients as well as coordinate the study and maintain the databank. The University is a world leader in research and treatment of Huntington's and other neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease). The trial is being run through the Department of Neurology's Clinical Trials Coordination Center and the Division of Experimental Therapeutics, where physicians are trained to design and interpret studies of potential new treatments to these diseases.