Thursday, March 22, 2007
NIH Phase III Trial Looks at Whether Creatine May Slow Disease Progression
Neurologists at the University of Maryland School of Medicine are participating in a large-scale national clinical trial to learn if the nutritional supplement creatine can slow the progression of Parkinson’s disease. Creatine is widely thought to improve exercise performance, but it is not an approved therapy for Parkinson’s disease or any other condition. Creatine’s potential benefit for Parkinson’s patients emerged from earlier trials from the National Institutes of Health (NIH) that employed a new rapid method for screening potential compounds.
“Right now, we have many good drugs to control Parkinson’s symptoms, but nothing to prevent those symptoms from getting worse. Finding a drug that can slow the disease’s progression is challenging,” says primary investigator Lisa M. Shulman, M.D., associate professor of neurology at the University of Maryland School of Medicine and a Parkinson’s disease specialist at the University of Maryland Medical Center.
“For this type of research, we need to study a large group of patients over a long period of time. The NIH-funded study of creatine is a new type of study, and we are pleased to continue our participation in this unprecedented national effort,” adds Dr. Shulman.
The double-blind, placebo-controlled, phase III study is one of the largest Parkinson’s disease clinical trials to date. The University of Maryland School of Medicine, which participated in the earlier phases of this study, is one of 51 sites in the United States and Canada that will be recruiting patients as part of an effort to enroll 1,720 people with Parkinson’s disease.
“This study is an important step. We are pleased to have so many sites participating in this study, which may help us move more quickly toward developing a therapy that could change the course of this devastating disease," says Elias A. Zerhouni, M.D., director of the NIH. "The goal is to improve the quality of life for people with Parkinson's for a longer period of time than is possible with existing therapies."
This is the first large study in a series of NIH-sponsored clinical trials called NIH Exploratory Trials in Parkinson's Disease (NET-PD). The University of Maryland School of Medicine has been affiliated with the program since 2003. The NIH organized this large network of sites to allow researchers to work with Parkinson’s disease patients over a long period of time, with a goal of finding effective and lasting treatments. NET-PD builds on a developmental research process, from laboratory research to pilot studies in a select group of patients to the definitive phase III trial of effectiveness in people with Parkinson’s disease.
“This study is an example of our commitment to Parkinson’s research,” said Story C. Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke, the NIH institute leading the study. “We are trying to explore every possible option for reducing the burden of this disease.”
Parkinson’s disease is a degenerative disorder of the brain in which patients develop such symptoms as progressive tremor, slowness of movements and muscle stiffness. It affects at least one million people in the United States. Although certain drugs, such as levodopa, can reduce the symptoms of Parkinson’s disease, there are no proven treatments that can slow the progressive deterioration in function.
Creatine is marketed as a nutritional supplement. Studies have suggested that it can improve the function of mitochondria, structures inside cells that produce energy. It also may act as an antioxidant that prevents damage from compounds that are harmful to cells in the brain. In a mouse model of Parkinson’s disease, creatine is able to prevent loss of the cells that are typically affected.
The study will enroll people who have been diagnosed with Parkinson’s disease within the past five years and who have been treated for two years or less with levodopa or other drugs that increase the levels of dopamine in the brain. Many of the symptoms of Parkinson’s disease result from the loss of dopamine, a neurotransmitter that helps to control movement. Half of the participants will receive creatine and half will receive a placebo. Neither the participants nor their doctors will know which treatment they receive.
The investigators will measure disease progression using standard rating scales that measure quality of life, walking ability, cognitive function and the ability to carry out other activities of daily living.
“For Parkinson’s patients, even simple tasks like walking or getting dressed become more difficult, and sometimes impossible, as the disease progresses. Through the NET-PD trials, we hope we can find a way to stop this progression, which would have a major effect on the lives of Parkinson’s patients,” adds Dr. Shulman, who is also the co-director of the Parkinson’s Disease and Movement Disorders Center at the University of Maryland Medical Center.