A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.

Caroline Greenan,Affect Investigators ,Rachel Canning,Elizabeth Coulthard,Clive Holmes,Sylvia Wallach,Catherine Henderson,Peter Passmore,Ly-Mee Yu,Bernadette Mcguinness,Lynn Murphy,Clive Ballard,Robert Stewart,Anne Corbett,Philip M Bath ,Frank Arrojo ,Peter Connelly,Martín Knapp ,Rob Jones,Michael O’sullivan ,Alan Thomas,Patrick Gavin Kehoe

doi:10.1186/s13063-016-1449-3

Abstract

BackgroundVascular 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.Methods/DesignThis 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.DiscussionThere 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.Trial registrationCurrent Controlled Trials ISRCTN31208535. Registered on 7 March 2014.

Highlights

Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments
This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established Subcortical ischaemic vascular dementia (SIVD)
It is estimated that the numbers of people with vascular dementia (VaD) and SIVD will increase globally in the future and the results of this study should inform important treatment decisions

Summary

Discussion

Vascular dementia is a very common cause of dementia syndromes. There are no treatments licensed for VaD and there is an urgent need for intervention studies in this condition. Abbreviations AD, Alzheimer’s disease; ADL, activities of daily living; AE, adverse event; ARWMC, age-related white matter changes; BHSCT, Belfast Health and Social Care Trust; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CCB, calcium channel blocker; CEA, cost-effectiveness analyses; CGIC, clinical global impression of change; CI, Chief Investigator; CONSORT, Consolidated Standards of Reporting Trials; CRF, case report form; CSRI, client service receipt inventory; CT, computed tomography; CTU, clinical trials unit; DAD, disability assessment in dementia; DEMQOL, dementia quality of life; DMEA committee, Diagnostic Monitoring and Events Adjudication committee; DMEC, Data Monitoring and Ethics Committee; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; ECG, electrocardiogram; EQ-5D, EuroQol group 5 dimensions health questionnaire; GCP, good clinical practice; GHQ-12, 12-item general health questionnaire; GP, general practitioner; IMP, investigational medicinal product; ISRCTN, International Standard Randomised Controlled Trial Number Register; ITT, intention-to-treat; MRI, magnetic resonance imaging; NICTU, Northern Ireland Clinical Trials Unit; NPI-D, neuropsychiatric inventory caregiver distress; PC-CTU, Primary Care Clinical Trials Unit; PI, Principal Investigator; QALY, quality-adjusted life-years; SAE, serious adverse event; SIVD, subcortical ischaemic vascular dementia; sMMSE, standardised Mini-Mental State Examination; SPC, summary of product characteristics; SUSAR, suspected unexpected serious adverse reaction; TICS-M, modified telephone interview for cognitive status; TMG, Trial Management Group; TSC, Trial Steering Committee; UAR, unexpected adverse reaction; VaD, vascular dementia; VADAS-cog, vascular dementia assessment scale cognitive subscale

Background

Findings