Parkinson's Disease (PD) is a progressive, debilitating neurodegenerative disorder, which is characterized clinically by tremor, rigidity, bradykinesia and postural instability. Eventually, PD leads to profound functional disability in th areas of employability, ambulation and self-care. While current estimates indicate that approximately six million people worldwide (over 1/2 million Americans) have been diagnosed PD, there is neither a treatment to slow progression nor a cure. Morbidity and mortality associated with PD burden results in an estimated six billion dollars in healthcare costs in the United States annually. The NET-PD program established an innovative, evidence-based process by which potential therapies were selected and tested for slowing of PD progression. Operationally, NET-PD is organized into a Clinical Coordinating Center (CCC) at the University of Rochester, a Statistical Coordinating Center (SCC) at the University of Texas School of Public Health, and clinical sites (US and Canada). The NET-PD network is currently conducting a Phase 3 randomized, double-blinded and placebo-controlled clinical trial of creatine (LSI), and a futility trial of pioglitazone (FS-ZONE). FS-ZONE is fully funded by prior grants and is described in this application in order to provide a full view of NET-PD activities, but no additionl funds are being requested. LS-1 is an innovative trial which will test the utility of creatine in a real-world setting. At this point the trail is fully enrolled, and the most critical factor in the success of this trial is the retention of the subjects through the course of the study and accurate and complete data collection. UAB enrolled the largest single number of subjects in the LS-1 trial (61), and has 45 subjects currently active. Retaining this group in LS-1 will be highly significant in determining the success of the overall trial effort. UAB provides a unique and highly supportive environment for the continued success of the NET-PD program, and continued participation of UAB as a study site will help to ensure successful completion of this important effort.