A phase ii trial of tideglusib in alzheimer's ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
A phase ii trial of tideglusib in alzheimer's disease
Auteur(s) :
Lovestone, Simon [Auteur]
Boada, Merce [Auteur]
Dubois, Bruno [Auteur]
Hull, Michael [Auteur]
Rinne, Juha O. [Auteur]
Huppertz, Hans-Jurgen [Auteur]
Calero, Miguel [Auteur]
Andres, Maria V. [Auteur]
Gomez-Carrillo, Belen [Auteur]
Leon, Teresa [Auteur]
Del Ser, Teodoro [Auteur]
Boada, Merce [Auteur]
Dubois, Bruno [Auteur]
Hull, Michael [Auteur]
Rinne, Juha O. [Auteur]
Huppertz, Hans-Jurgen [Auteur]
Calero, Miguel [Auteur]
Andres, Maria V. [Auteur]
Gomez-Carrillo, Belen [Auteur]
Leon, Teresa [Auteur]
Del Ser, Teodoro [Auteur]
Titre de la revue :
Journal of Alzheimer's disease . JAD
Nom court de la revue :
J. Alzheimers Dis.
Numéro :
45
Pagination :
75-88
Date de publication :
2015-01-01
ISSN :
1875-8908
Mot(s)-clé(s) en anglais :
randomized controlled clinical trial
Alzheimer''s disease
GSK-3
pharmacological treatment
tideglusib
Alzheimer''s disease
GSK-3
pharmacological treatment
tideglusib
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
BACKGROUND: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD).
OBJECTIVE: To prove the clinical efficacy of an inhibitor of glycogen synthase ...
Lire la suite >BACKGROUND: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). OBJECTIVE: To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. METHODS: Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. RESULTS: 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. CONCLUSIONS: Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients.Lire moins >
Lire la suite >BACKGROUND: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). OBJECTIVE: To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. METHODS: Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. RESULTS: 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. CONCLUSIONS: Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
CNRS
Inserm
Université de Lille
CNRS
Inserm
Université de Lille
Collections :
Équipe(s) de recherche :
Troubles cognitifs dégénératifs et vasculaires
Date de dépôt :
2019-11-27T13:36:15Z