Laurène Leclair-Visonneau1, Tiphaine Rouaud2, Bérangère Debilly3, Franck Durif3, Jean-Luc Houeto4, Alexandre Kreisler5, Luc Defebvre5, Estelle Lamy2, Christelle Volteau6, Jean-Michel Nguyen6, Séverine Le Dily7, Philippe Damier2, Claire Boutoleau-Bretonnière2, Pascal Lejeune8, Pascal Derkinderen9. 1. 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. 2. Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France. 3. CHU Clermont-Ferrand, Department of Neurology, Clermont-Ferrand F-63001, France. 4. CHU Poitiers, Department of Neurology, Poitiers F-86000, France. 5. CHU Lille, Department of Neurology, Lille F-59000, France. 6. CHU Nantes, Pôle d'Information Médicale, Évaluation et Santé Publique (PIMESP), Nantes F-44093, France. 7. Inserm, CIC-04, Nantes F-44093, France. 8. CHD La Roche Sur Yon, Department of Neurology, La Roche Sur Yon, F-85000, France. 9. Inserm, CIC-04, Nantes F-44093, France; CHU Nantes, Department of Neurology, Nantes F-44093, France. Electronic address: derkinderenp@yahoo.fr.
Abstract
OBJECTIVES: 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). PATIENTS AND METHODS: We performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500mg/day) ormatching 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. CONCLUSION: Our results suggest that VPA is not effective as a disease-modifying agent in PSP.
RCT Entities:
OBJECTIVES: 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). PATIENTS AND METHODS: We performed a double-blind, randomized, placebo-controlled trial, in 28 PSPpatients 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. CONCLUSION: Our results suggest that VPA is not effective as a disease-modifying agent in PSP.
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