The NIH Exploratory Trials in Parkinson's Disease (NET-PD) program was established to facilitate the development of therapies to slow the progression of this chronic neurodegenerative disease. This network effectively executed futility studies of candidate therapies, which identified creatine as a having therapeutic potential. A subsequent Phase 3 efficacy trial, known as Long-term Study 1 (LS1) was designed and is being executed to evaluate the efficacy of creatine in slowing clinical decline in Parkinson's Disease (PD). LS1 is currently operational and has successfully met recruitment goals. Participants are being followed for a minimum of 5 years and maximum of 8 years. As a result, the final study visits will occur between June 2014 and May 2015. The current application requests funds to carry out Clinical Coordination Center activities through the completion of the NET-PD trials. These activities are guided by the following specific aims.
Specific Aim 1 is to complete follow-up and enhance retention of enrolled participants in LS1 in order to test the primary hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD against the background of dopaminergic therapy and best PD care.
Specific Aim 2 is to perform secondary analyses to evaluate the efficacy of creatine on individual PD clinical measures between baseline and the final follow-up visit that encompasses 5-8 years of study participation, as well as analyses of overall safety and tolerability.
Specific Aim 3 is to continue to operate a Clinical Coordination Center for the completion of NET-PD studies, which involves (a) maintenance of study protocols, (b) Clinical Site oversight and training, (c) maintenance of quality and regulatory standards, (d) logistical oversight of experimental treatment distribution to Clinical Sites, (e) receipt and management of all clinical trial data, (f) close out the database and transfer to the Statistical Coordination Ceter for analysis, (g) participation in the analysis plans, interpretation and reporting of the trial reults, and (h) assisting the Statistical Coordinating Center in documenting and archiving the data in a publicly available database.
Specific Aim 4 is to maintain an administrative structure that allows close collaboration with the Statistical Coordination Center, the Clinical Sites, NINDS Scientific Program personnel, the NINDS Data and Safety Monitoring Board and the NINDS Oversight Committee. Successful completion of these aims will achieve the goal of the NET-PD program to establish an innovative, evidence-based process by which potential therapies are selected and tested for slowing of PD progression.
The accumulated disability that PD causes is a major source of diminished quality of life and increased health care costs. Despite the advances in our understanding of the pathophysiology in PD, there are no current therapies that slow the inexorable clinical decline. LS1 will help to determine if creatine can slow clinical decline and provide better information on the course of early PD than is currently available. 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.
|Luo, Sheng; Lawson, Andrew B; He, Bo et al. (2016) Bayesian multiple imputation for missing multivariate longitudinal data from a Parkinson's disease clinical trial. Stat Methods Med Res 25:821-37|
|He, Bo; Luo, Sheng (2016) Joint modeling of multivariate longitudinal measurements and survival data with applications to Parkinson's disease. Stat Methods Med Res 25:1346-58|
|Wills, Anne-Marie A; PÃ©rez, 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|
|Luo, Sheng; Chan, Wenyaw; Detry, Michelle A et al. (2016) Binomial regression with a misclassified covariate and outcome. Stat Methods Med Res 25:101-17|
|Simon, David K; Simuni, Tanya; Elm, Jordan et al. (2015) Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects. J Parkinsons Dis 5:731-6|
|Augustine, Erika F; PÃ©rez, Adriana; Dhall, Rohit et al. (2015) Sex Differences in Clinical Features of Early, Treated Parkinson's Disease. PLoS One 10:e0133002|
|Chen, Yong; Chu, Haitao; Luo, Sheng et al. (2015) Bayesian analysis on meta-analysis of case-control studies accounting for within-study correlation. Stat Methods Med Res 24:836-55|
|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|
|Chen, Yong; Luo, Sheng; Chu, Haitao et al. (2014) An Empirical Bayes Method for Multivariate Meta-analysis with an Application in Clinical Trials. Commun Stat Theory Methods 43:3536-3551|
Showing the most recent 10 out of 43 publications