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 plast...

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Vydáno v:	Current controlled trials in cardiovascular medicine Ročník 20; číslo 1; s. 191 - 10
Hlavní autoři:	Femminella, Grazia Daniela, Frangou, 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, Brooks, David J., Passmore, Anthony Peter, Ballard, Clive, Edison, Paul
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 03.04.2019 BioMed Central Ltd Springer Nature B.V BMC
Témata:	Activities of Daily Living Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer Disease - physiopathology Alzheimer Disease - psychology Alzheimer's disease Antidiabetics Apoptosis Batteries Biomarkers Biomedicine Brain Brain - drug effects Brain - metabolism Brain - physiopathology Brain research Care and treatment Cell growth Cerebral glucose metabolic rate Clinical trials Clinical Trials, Phase II as Topic Cognition & reasoning Cognition - drug effects Dementia Development and progression Diabetes Double-Blind Method Drug dosages Genetic engineering Glucagon Glucagon-Like Peptide-1 Receptor - metabolism Glucagon-Like Peptide-1 Receptor Agonists Glucose Glucose - metabolism Growth factors Health Sciences Humans Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use Insulin Liraglutide Liraglutide - adverse effects Liraglutide - therapeutic use Medical research Medicine Medicine & Public Health Memory Memory - drug effects Metabolism Morbidity Multicenter Studies as Topic Neurons Neuroprotective Agents - adverse effects Neuroprotective Agents - therapeutic use Obesity Oligomers Peptides Phosphorylation Physiology Proteins Randomised controlled trial Randomized Controlled Trials as Topic Severity of Illness Index Statistics for Life Sciences Study Protocol Time Factors Tomography Treatment Outcome Type 2 diabetes United Kingdom United Kingdom Cerebral glucose metabolic rate Alzheimer’s disease Liraglutide Randomised controlled trial Dementia
ISSN:	1745-6215, 1745-6215
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1745-6215 1745-6215
DOI:	10.1186/s13063-019-3259-x