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. 2012 Oct;27(12):1513-21. doi: 10.1002/mds.25175.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antipsychotic Agents / therapeutic use*
  • Canada
  • Creatine / therapeutic use*
  • Double-Blind Method
  • Evidence-Based Medicine*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • National Institute of Neurological Disorders and Stroke (U.S.)
  • Outcome Assessment, Health Care
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / psychology
  • Quality of Life
  • Severity of Illness Index
  • Statistics, Nonparametric
  • United States

Substances

  • Antipsychotic Agents
  • Creatine

Grant support