This site uses cookies to measure how you use the website so it can be updated and improved based on your needs and also uses cookies to help remember the notifications you’ve seen, like this one, so that we don’t show them to you again. If you could also tell us a little bit about yourself, this information will help us understand how we can support you better and make this site even easier for you to use and navigate.

A phase II trial of tideglusib in Alzheimer’s disease


Lovestone, Simon, Boadab, Mercè, Dubois, Bruno, Hüll, Michael, Rinne, Juha O., Huppertz, Hans-Jürgen, Calero, Miguel, Andrés, María V., Gómez-Carrillo, Belén, Leon, Teresa, del Seri, Teodoro


Journal of Alzheimer's Disease, Volume: 45, No.: 1, Pages.: 75-88

Year of Publication



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. (PsycINFO Database Record (c) 2015 APA, all rights reserved). (journal abstract)


alzheimer’s disease, clinical trials, drug therapy, gsk3, magnetic resonance imaging, pharmacological treatment, placebo, randomized controlled clinical trial, tideglusib

Countries of Study

Finland, France, Germany, Spain, UK

Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

ADLs/IADLs, Behaviour, Cognition, Quality of Life of Person With Dementia

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime