Creatine is an amino acid frequently used by athletes to increase their muscle bulk and is also marketed for improving exercise performance.
The National Institutes of Health (NIH) study on the compound's potential for easing Parkinson's disease symptoms is set to involve 1720 people.
If results are positive, the trial could spell new marketing directions and opportunities for creatine formulators.
In the United States, 1.5 million people have Parkinson's - according to the National Parkinson Foundation - with 60,000 new cases diagnosed each year.
The brain disorder's debilitating symptoms include shaking, slowness of movement, stiffness and difficulty with balance.
NIH's double-blind, placebo-controlled, phase III study will be one of the largest Parkinson's (PD) clinical trials to date - involving patients with early-stages of the disease from 51 medical centers in the United States and Canada.
"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," said Dr. John Marler, NINDS associate director for clinical trials.
Participants will take part for five to seven years in the study, which will be led by the University of Rochester in New York and the Medical University of South Carolina in Charleston.
Movement disorders specialists will see patients at sites across North America as part of the trial.
"We are studying a stage of the disease that usually hasn't been included in clinical studies," said study leader, Dr. Karl Kieburtz from the University of Rochester.
The study is designed to include a broad range of people and investigators will measure disease progression by measuring quality of life, ability to walk and cognitive function.
Creatine, which occurs naturally in foods like fish and red meat, is banned in some countries because of studies showing a possible link between long-term supplementation and increased cancer risk.
It is not banned by the International Olympic Committee, which classifies it as food.
The amino acid is sold as a dietary supplement in liquid, tablet and powder forms, chiefly in the form of creatine monohydrate.