The double-blind, placebo-controlled, phase III study is one of the largest PD clinical trials to date. It will enroll 1720 people with early-stage PD at 51 medical centers in the United States and Canada.
"This study is an important step 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." Currently there is no treatment that has been shown to slow the progression of PD.
The trial is the first large study in a series of NINDS-sponsored clinical trials called NET-PD (NIH Exploratory Trials in Parkinson's Disease). NINDS has organized this large network of sites to allow researchers to work with PD 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 the Institute's commitment to Parkinson's research," says NINDS director Story C. Landis, Ph.D. "We are trying to explore every possible option for reducing the burden of this disease."
Participants will be in the phase III study for five to seven years. The effort will be led by Ka rl Kieburtz, M.D., M.P.H., of the University of Rochester in New York, and Barbara C. Tilley, Ph.D., of the Medical University of South Carolina in Charleston, and the patients will be seen by movement disorders specialists at the NET-PD sites across the United States and Canada.
PD is a degenerative disorder of the brain in which patients develop symptoms such as progressive tremor, slowness of movements, and stiffness of muscles. It affects at least one million people in the United States. Although certain drugs, such as levodopa, can reduce the symptoms of PD, 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, which produce energy inside cells. 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 PD, creatine is able to prevent loss of the cells that are typically affected.
"Creatine, or any compound that may slow the progression of PD, could have very important long-term benefits for people who are living with this disease," says John R. Marler, M.D., NINDS associate director for clinical trials.
The study will enroll people who have been diagnosed with PD 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 PD 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.
"We are studying a stage of the disease that usually hasn't been included in clinical studies," notes Dr. Kieburtz. The study is designed to include a broad range of people, with special efforts to recruit a diverse population that is similar to the makeup of the population with PD in the United States.
The investigators will measure disease progression using standard rating scales that measure quality of life, ability to walk, cognitive function, and the ability to carry out other activities of daily living.