title: A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
abstract: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia.
  
  
  
  This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks.
  
  
  
  There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions.
  
  
  
  Current Controlled Trials ISRCTN31208535 . Registered on 7 March 2014.
authors.affiliation: Northern Ireland Clinical Trials Unit, 1st Floor Elliott Dynes Building, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Greenan
authors.affiliation: Northern Ireland Clinical Trials Unit, 1st Floor Elliott Dynes Building, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Primary Care Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences (Gibson Building), Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.
authors.forename: Ly-Mee
authors.initials: LM
authors.lastname: Yu
authors.affiliation: Dementia Research Group, Clinical Neurosciences, University of Bristol, Level 1 Learning and Research Building, Bristol, BS10 5NB, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: Dementia Research Group, Clinical Neurosciences, University of Bristol, Level 1 Learning and Research Building, Bristol, BS10 5NB, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Coulthard
authors.affiliation: Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Bath
authors.affiliation: Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.affiliation: School of Community Health Sciences, Division of Psychiatry, Institute of Mental Health, University of Nottingham, Innovation Park, Triumph Road, Nottingham, NG7 2TU, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Jones
authors.affiliation: Wolfson CARD, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Corbett
authors.affiliation: Biomedical Research Building, Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Murray Royal Hospital, Muirhall Road, Perth, PH2 7BH, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Connelly
authors.affiliation: Research Network Volunteer, Alzheimer's Society, 58 St Katharine's Way, London, E1W 1LB, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Arrojo
authors.affiliation: Research Network Volunteer, Alzheimer's Society, 58 St Katharine's Way, London, E1W 1LB, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Canning
authors.affiliation: Research Network Volunteer, Alzheimer's Society, 58 St Katharine's Way, London, E1W 1LB, UK.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wallach
authors.affiliation: Personal Social Services Research Unit (PSSRU), London School of Economics, Houghton Street, London, WC2A 2AE, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Henderson
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queen's University Belfast, The Royal Hospitals, Grosvenor Road, Belfast, BT12 6BA, UK.
authors.forename: Bernadette
authors.initials: B
authors.lastname: McGuinness
authors.affiliation: Academic Neuroscience Centre, Institute of Psychiatry, De Crespigny Park, PO Box 41, London, SE5 8AF, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: O'Sullivan
authors.affiliation: MARC, University of Southampton, Moorgreen Hospital, Botley Road, Southampton, S030 3JB, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.affiliation: Personal Social Services Research Unit (PSSRU), London School of Economics, Houghton Street, London, WC2A 2AE, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Knapp
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London, SE1 1UL, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queen's University Belfast, The Royal Hospitals, Grosvenor Road, Belfast, BT12 6BA, UK. p.passmore@qub.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Passmore
mesh_terms: D000203:Activities of Daily Living; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011788:Quality of Life; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine
keywords: Amlodipine; Calcium channel blockade; Cognitive outcome; Subcortical ischaemic vascular dementia; Vascular dementia