title: Randomized placebo-controlled trial of sodium valproate in progressive supranuclear palsy.
abstract: OBJECTIVE
  Results from preclinical studies suggest that inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for tauopathies. The aim of the present study was therefore to determine the effects of sodium valproate (VPA), a GSK-3 inhibitor, on disease progression in progressive supranuclear palsy (PSP).
  
  
  METHODS
  We performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500mg/day) or matching placebo for 24 months. The primary endpoint was the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 12 and 24 months. Secondary endpoints evaluated the effects of VPA on cognitive and behavioral status (MMSE, Mattis Dementia Rating Scale, Wisconsin Card Sorting, Gröber and Buschke and Oral Denomination 80 tests), tolerability of treatment, and patient compliance.
  
  
  RESULTS
  There were no baseline differences between active treatment and placebo groups in age and clinical rating scores. PSPRS score at 12 months was significantly higher in the VPA than in the placebo group (60.8±20 versus 46.9±18.6 respectively, p=0.01), but was similar between the two groups at 24 months. No significant differences were observed between VPA and placebo groups for the secondary endpoints.
  
  
  CONCLUSIONS
  Our results suggest that VPA is not effective as a disease-modifying agent in PSP.
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France; CHU Nantes, Department of Physiology, Nantes F-44093, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Leclair-Visonneau
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Rouaud
authors.affiliation: CHU Clermont-Ferrand, Department of Neurology, Clermont-Ferrand F-63001, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Debilly
authors.affiliation: CHU Clermont-Ferrand, Department of Neurology, Clermont-Ferrand F-63001, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.affiliation: CHU Poitiers, Department of Neurology, Poitiers F-86000, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Houeto
authors.affiliation: CHU Lille, Department of Neurology, Lille F-59000, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kreisler
authors.affiliation: CHU Lille, Department of Neurology, Lille F-59000, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Defebvre
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Lamy
authors.affiliation: CHU Nantes, Pôle d'Information Médicale, Évaluation et Santé Publique (PIMESP), Nantes F-44093, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Volteau
authors.affiliation: CHU Nantes, Pôle d'Information Médicale, Évaluation et Santé Publique (PIMESP), Nantes F-44093, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France.
authors.forename: Séverine Le
authors.initials: SL
authors.lastname: Dily
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Boutoleau-Bretonnière
authors.affiliation: CHD La Roche Sur Yon, Department of Neurology, La Roche Sur Yon, F-85000, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lejeune
authors.affiliation: Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France. Electronic address: derkinderenp@yahoo.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013494:Supranuclear Palsy, Progressive / Q000188:drug therapy*; D017211:Treatment Failure; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid
keywords: Controlled-trial; Neuroprotection; Progressive supranuclear palsy; Sodium valproate