J Jankovic1, C Hunter. 1. Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 6550 Fannin Smith 1801, Houston, TX 77030, USA. josephj@bcm.tmc.edu
Abstract
BACKGROUND: To the extent that excitotoxicity may play a role in the pathogenesis of certain neurodegenerative disorders, antagonists of glutamate, an excitatory neurotransmitter, should exert neuroprotective effects in these disorders, including Parkinson's disease (PD). METHODS:Patients in early stages of PD, not previously treated withlevodopa, were randomized to receive riluzole 50mg capsules orally, taken twice daily or a matching placebo. All subjects were evaluated at baseline (pre-treatment), at 1, 3 and 6 months (post-treatment), and following a 6-week washout. After the washout, all subjects were offered an enrollment in an open label, 1-year, extension study. The principal investigator (JJ), however, remained blinded to the original assignment during the entire study. The patients were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hoehn & Yahr (HY) stage, and Schwab and England (SE) ADL scale. The quantitative assessments included Movement Time (MT) and Reaction Time (RT). Additionally, the time to initiate dopaminergic therapy was assessed. Safety was determined at each visit by clinical history and examination, a panel of blood safety laboratory tests including complete blood count, chemistry profile, and liver function studies. RESULTS:Twenty patients with a mean age of 62+/-9.02 (range: 46-73) years and mean duration of symptoms of 18+/-9.53 (range: 6-36) months were enrolled. One patient withdrew from the study because he needed more aggressive treatment of his symptoms. Analysis of the efficacy variables showed no meaningful symptomatic effect of riluzole on UPDRS score. Likewise, there was no significant change in the median HY stage, SE ADL rating, or the MT/RT. Seventeen patients (mean age 62+/-9.26) elected to continue in the open label extension study. Although the observed deterioration in UPDRS scores seemed to be more pronounced in the placebo group than in the riluzole group, the difference did not reach statistical significance. There was no statistically significant difference in the latency between enrollment and start of symptomatic therapy when patients initially treated with riluzole were compared to those initially treated with placebo (8.3 vs 9 months). CONCLUSIONS: This pilot and extension study showed that riluzole, 100mg/day, was well tolerated in patients with early PD. No evidence of symptomatic effect of riluzole was observed. Because of the exploratory nature of the design and small size of the study, it was not possible to determine whether riluzole affected the natural history of PD. The encouraging results from our study, however, suggest that larger, longitudinal studies are warranted.
RCT Entities:
BACKGROUND: To the extent that excitotoxicity may play a role in the pathogenesis of certain neurodegenerative disorders, antagonists of glutamate, an excitatory neurotransmitter, should exert neuroprotective effects in these disorders, including Parkinson's disease (PD). METHODS:Patients in early stages of PD, not previously treated with levodopa, were randomized to receive riluzole 50mg capsules orally, taken twice daily or a matching placebo. All subjects were evaluated at baseline (pre-treatment), at 1, 3 and 6 months (post-treatment), and following a 6-week washout. After the washout, all subjects were offered an enrollment in an open label, 1-year, extension study. The principal investigator (JJ), however, remained blinded to the original assignment during the entire study. The patients were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hoehn & Yahr (HY) stage, and Schwab and England (SE) ADL scale. The quantitative assessments included Movement Time (MT) and Reaction Time (RT). Additionally, the time to initiate dopaminergic therapy was assessed. Safety was determined at each visit by clinical history and examination, a panel of blood safety laboratory tests including complete blood count, chemistry profile, and liver function studies. RESULTS: Twenty patients with a mean age of 62+/-9.02 (range: 46-73) years and mean duration of symptoms of 18+/-9.53 (range: 6-36) months were enrolled. One patient withdrew from the study because he needed more aggressive treatment of his symptoms. Analysis of the efficacy variables showed no meaningful symptomatic effect of riluzole on UPDRS score. Likewise, there was no significant change in the median HY stage, SE ADL rating, or the MT/RT. Seventeen patients (mean age 62+/-9.26) elected to continue in the open label extension study. Although the observed deterioration in UPDRS scores seemed to be more pronounced in the placebo group than in the riluzole group, the difference did not reach statistical significance. There was no statistically significant difference in the latency between enrollment and start of symptomatic therapy when patients initially treated with riluzole were compared to those initially treated with placebo (8.3 vs 9 months). CONCLUSIONS: This pilot and extension study showed that riluzole, 100mg/day, was well tolerated in patients with early PD. No evidence of symptomatic effect of riluzole was observed. Because of the exploratory nature of the design and small size of the study, it was not possible to determine whether riluzole affected the natural history of PD. The encouraging results from our study, however, suggest that larger, longitudinal studies are warranted.
Authors: Paul C Trippier; Kristin Jansen Labby; Dustin D Hawker; Jan J Mataka; Richard B Silverman Journal: J Med Chem Date: 2013-03-27 Impact factor: 7.446
Authors: Christopher Pittenger; Vladimir Coric; Mounira Banasr; Michael Bloch; John H Krystal; Gerard Sanacora Journal: CNS Drugs Date: 2008 Impact factor: 5.749