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.
Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care.
Division of Biostatistics and Epidemiology, Medical University of South Carolina, 135 Cannon Street, Suite 303, PO Box 250835, Charleston, SC 29425, USA. elmj@musc.edu
Jordan J
JJ
Elm
D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002170:Canada; D003401:Creatine / Q000627:therapeutic use*; D004311:Double-Blind Method; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014481:United States
D014150:Antipsychotic Agents; D003401:Creatine