Parkinson's disease is an inexorably progressive disorder of unknown cause in which neurons of the substantia nigra progressively degenerate resulting in ever greater degrees of brain dopamine deficiency. While a number of treatments have been developed that improve the neurochemical deficit, no treatment has been demonstrated in humans that delays the progression of the disease (as distinguished from masking symptoms). Such an effect is highly desirable because if this could be achieved, a significant delay in clinical deterioration of patients could be realized. This competitive continuation proposal aims to continue UT Southwestern Medical Center as a Clinical Site for ongoing conduct of the NET-PD clinical trials. These include the ongoing LS-1 study and FS-ZONE study. LSI is a 5 year double-blind, placebo controlled investigation of creatine as a possible disease-modifying agent for PD. FS-ZONE is a 44 week futility trial assessing pioglitazone as a possible disease-modifying agent for PD. UT Southwestern Medical Center in Dallas, TX is well suited to continuing its work as a Clinical Site of the NET-PD network. It functions as the primary academic referral center for North Texas, and its four staff neurologists are experienced in the design, conduct, and reporting of clinical trials in Parkinson's disease. If funded, the site will continue its active follow-up of te 49 subjects currently enrolled in the NET-PD LS1 trial and will continue to recruit and follow subjects for the ongoing FS-ZONE study. While it is unclear if either agent under study will slow the progression of PD, this unique network of clinical research centers is ideally suited to perform large scale, long duration, scientifically sound clinical trials that have great promise fo ultimately discovering a drug or drugs that can slow the degenerative process of PD.
The search for a disease modifying treatment for PD is of paramount importance because by slowing disease progression; disability can be reduced and patient quality of life can be improved. These studies have the best chance of discovering such an agent due to the large size of the study population and the rigorous clinical trial methodology being employed. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation; based upon the group's discussion; there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore; the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.
|Wills, Anne-Marie A; Pérez, Adriana; Wang, Jue et al. (2016) Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1 JAMA Neurol 73:321-8|
|NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators (2015) Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol 14:795-803|
|Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators; Kieburtz, Karl; Tilley, Barbara C et al. (2015) Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA 313:584-93|
|Umeh, Chizoba C; Pérez, Adriana; Augustine, Erika F et al. (2014) No sex differences in use of dopaminergic medication in early Parkinson disease in the US and Canada - baseline findings of a multicenter trial. PLoS One 9:e112287|
|Elm, Jordan J; NINDS NET-PD Investigators (2012) Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1. Mov Disord 27:1513-21|
|Elble, Rodger J; Suchowersky, Oksana; Shaftman, Stephanie et al. (2010) Impact of belief in neuroprotection on therapeutic intervention in Parkinson's disease. Mov Disord 25:1082-6|
|Schneider, Jay S; Elm, Jordan J; Parashos, Sotirios A et al. (2010) Predictors of cognitive outcomes in early Parkinson disease patients: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience. Parkinsonism Relat Disord 16:507-12|