Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease:Study protocol for a randomised controlled trial (ELAD study)


Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. Methods/design: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale - Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study - Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment. Trial registration: ClinicalTrials.gov, NCT01843075. Registration 30 April 2013.

Publication DOI: https://doi.org/10.1186/s13063-019-3259-x
Divisions: College of Health & Life Sciences > Aston Medical School
Funding Information: This article presents independent research sponsored by Imperial College London and supported by the NIHR, CRF, and BRC at the Imperial College Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of Imperial Colleg
Additional Information: © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords: Alzheimer's disease,Cerebral glucose metabolic rate,Dementia,Liraglutide,Randomised controlled trial,Medicine (miscellaneous),Pharmacology (medical)
Publication ISSN: 1745-6215
Last Modified: 27 Feb 2024 08:13
Date Deposited: 29 Apr 2019 08:14
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-04-03
Accepted Date: 2019-02-27
Authors: Femminella, Grazia Daniela
Frangou, Eleni
Love, Sharon B.
Busza, Gail
Holmes, Clive
Ritchie, Craig
Lawrence, Robert
McFarlane, Brady
Tadros, George (ORCID Profile 0000-0001-5820-7643)
Ridha, Basil H.
Bannister, Carol
Walker, Zuzana
Archer, Hilary
Coulthard, Elizabeth
Underwood, Ben R.
Prasanna, Aparna
Koranteng, Paul
Karim, Salman
Junaid, Kehinde
McGuinness, Bernadette
Nilforooshan, Ramin
Macharouthu, Ajay
Donaldson, Andrew
Thacker, Simon
Russell, Gregor
Malik, Naghma
Mate, Vandana
Knight, Lucy
Kshemendran, Sajeev
Harrison, John
Brooks, David J.
Passmore, Anthony Peter
Ballard, Clive
Edison, Paul



Version: Published Version

License: Creative Commons Attribution

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