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 52 medical centers in the U.S. and Canada. “This study is an important step toward developing a therapy that could change the course of this devastating disease,” said Elias Zerhouni, MD, 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.
Participants will be in the phase III study for five to seven years. The effort will be led by Karl Kieburtz, MD, MPH, of the University of Rochester in New York, and Barbara Tilley, PhD, 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 U.S. 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 U.S. 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. 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.
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.
Avicena Group, Inc., the company supplying the creatine and the placebo for the study, released a statement following NIH’s announcement of the creatine/Parkinson’s trial in an effort to clarify the difference between its compound, PD-02, and the common (nutritional supplement) form of creatine.
PD-02, the Parkinson's disease drug candidate being used in the Phase III clinical trial, the company maintains, is a unique creatine-based formulation that has been manufactured to strict FDA drug GMP guidelines. PD-02 is produced using a patented process that ensures a highly purified form of creatine without the harmful neurotoxins, such as cyanamide, which may be dangerous to patients with neurodegenerative diseases like Parkinson's. In addition, only this GMP drug formulation has been shown to be safe and well tolerated in high doses in previous clinical studies conducted by Dr. Kieburtz.
Dr. Kieburtz says there is a critical distinction between the pharmaceutical grade creatine formulation that is being used in this Parkinson's disease trial and the creatine that may be sold over-the-counter in retail stores. Therefore, he claims it is unwise for Parkinson's patients to conclude that the common form of creatine has any clinical benefits and recommends against using it.
Avicena’s CEO Belinda Tsao-Nivaggioli added, "We go to great lengths to ensure that Avicena's Parkinson's disease drug candidate, PD-02, is manufactured under the tightest FDA standards. Only as a result of these efforts, can the drug's purity as well as safety and efficacy profile be guaranteed."