DOMINO-AD protocol : donepezil and memantine in moderate to severe Alzheimer's disease – a multicentre RCT
. (2009) DOMINO-AD protocol : donepezil and memantine in moderate to severe Alzheimer's disease – a multicentre RCT. Trials, Vol.10 . Article 57. ISSN 1745-6215
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Official URL: http://dx.doi.org/10.1186/1745-6215-10-57
Background: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase
inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild
to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in
the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not
recommended by the England and Wales National Institute for Health and Clinical Excellence.
However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in
particular, what to do as the condition progresses from moderate to severe. Options include
continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase
inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to
establish the most effective drug option for people with AD who are progressing from moderate
to severe dementia despite treatment with donepezil.
Method: DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled
trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with
Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited.
Each is randomized to one of four treatment options: continuation of donepezil with memantine
placebo added; switch to memantine with donepezil placebo added; donepezil and memantine
together; or donepezil placebo with memantine placebo. 800 participants are being recruited and
treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities
of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive
dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and
DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using
Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline,
6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone
interview to record institutionalization.
Discussion: There is considerable debate about the clinical and cost effectiveness of anti-dementia
drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those
managing patients at a particularly important clinical transition point.
Trial registration: Current controlled trials ISRCTN49545035
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry|
|Divisions:||Faculty of Medicine > Warwick Medical School > Mental Health and Wellbeing
Faculty of Medicine > Warwick Medical School
|Library of Congress Subject Headings (LCSH):||Acetylcholinesterase, Methyl aspartate, Alzheimer's disease -- Treatment, Clinical pharmacology, Clinical trials -- Reporting -- Great Britain|
|Journal or Publication Title:||Trials|
|Publisher:||BioMed Central Ltd.|
|Official Date:||24 July 2009|
|Page Range:||Article 57|
|Access rights to Published version:||Open Access|
|Funder:||Medical Research Council (Great Britain) (MRC), Alzheimer’s Society (AS)|
1. Areosa SA, Sheriff F, McShane R: Memantine for dementia.
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