Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study)
Author
Femminella, Grazia DanielaFrangou, Eleni
Love, Sharon B
Busza, Gail
Holmes, Clive
Ritchie, Craig
Lawrence, Robert
McFarlane, Brady
Tadros, George
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
Hölscher, Christian
Brooks, David J
Passmore, Anthony Peter
Ballard, Clive
Edison, Paul
Publication date
2019-04-03
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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.Citation
Femminella GD, Frangou E, Love SB, Busza G, Holmes C, Ritchie C, Lawrence R, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood BR, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Harrison J, Hölscher C, Brooks DJ, Passmore AP, Ballard C, Edison P. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study). Trials. 2019 Apr 3;20(1):191. doi: 10.1186/s13063-019-3259-x. Erratum in: Trials. 2020 Jul 19;21(1):660. PMID: 30944040; PMCID: PMC6448216.Type
ArticlePMID
30944040Journal
TrialsPublisher
BMCae974a485f413a2113503eed53cd6c53
10.1186/s13063-019-3259-x
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