Condition category
Circulatory System
Date applied
21/06/2019
Date assigned
29/07/2019
Last edited
25/07/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
People affected by stroke report that memory and thinking problems are amongst their greatest concerns. Stroke and vascular dementia are closely related but traditionally have been studied as separate processes and this has delayed advances in knowledge and treatment. A more 'joined-up' study would help. Stroke patients are good at joining studies, and some blood vessel related treatments might help protect thinking and memory in future. A collaboration of experts in stroke and vascular dementia have worked with people affected by both diseases to create a program of work that answers fundamental questions: who will develop memory and thinking problems after stroke, why does this happen, how can we treat it?

Who can participate?
Patients aged 18 and over who attend hospital with a stroke of any type or ministroke

What does the study involve?
The researchers collect information about the person, their health, the stroke, assess their thinking and memory, and talk to their relatives. They use short or longer assessments at different stages after the stroke to avoid tiring the patient. Recovery, changing symptoms and thinking skills are assessed at about 6+/- 2 weeks after the first assessment and by post/telephone annually to 2 years and beyond. The researchers assess routinely collected brain scans and other routine tests, and where possible, do more blood tests or genetic analysis to work out what affects memory and thinking.

What are the possible benefits and risks of participating?
The study will provide much better information on how many patients thinking and memory are affected, how to identify them, their outlook for recovery. This will help to understand vessel mechanisms better, advise patients, and plan health services. Participants will be offered opportunities to join clinical trials as new treatments become ready for testing, to help avoid dementia in the future. The participants will get more detailed assessments of memory, thinking and mood than would happen in standard care. The results of these assessments and any other medically relevant results can also be shared with the hospital team or the participants’ GP, which may be useful to their care. Possible disadvantages of taking part include that some people may find these extra questions tiring and they will take up the participants’ time.

Where is the study run from?
1. Centre for Clinical Brain Sciences (UK)
2. NHS Greater Glasgow and Clyde (UK)
3. Nottingham University Hospitals NHS Trust (UK)
4. Salford Royal NHS Trust (UK)
5. University College London Hospitals NHS Trust (UK)
6. Cambridge University Hospitals NHS Trust (UK)
7. University Hospitals Leicester NHS Trust (UK)
8. Lancashire Teaching Hospital NHS Trust (UK)
9. Kings College Hospital NHS Trust (UK)
10. Oxford University Hospitals NHS Trust (UK)

When is the study starting and how long is it expected to run for?
July 2018 to June 2023

Who is funding the study?
Stroke Association (UK)

Who is the main contact?
Prof. Joanna Wardlaw
joanna.wardlaw@ed.ac.uk

Trial website

https://www-apache.nottingham.ac.uk/~nszwww/r4vad/live/r4vad_login.php?reason=auth

Contact information

Type

Scientific

Primary contact

Prof Joanna Wardlaw

ORCID ID

http://orcid.org/0000-0002-9812-6642

Contact details

Centre for Clinical Brain Sciences
Chancellor's Building
Little France Crescent
Edinburgh
EH16 4SB
United Kingdom
+44 (0)131 332 2943
joanna.wardlaw@ed.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

AC18001

Study information

Scientific title

Rates, Risks and Routes to Reduce Vascular Dementia

Acronym

R4VaD

Study hypothesis

To determine the rates of cognitive impairment and dementia to at least two years after stroke, across a wide range of patients, stroke severities and subtypes, stratified by patient-related (age, premorbid and prestroke cognition, socioeconomic status, vascular risk factors, lifestyle) and stroke-related (severity, ischaemic, haemorrhagic, lacunar vs non-lacunar, imaging findings) factors.

Ethics approval

1. Approved 09/07/2018, Scotland A Research Ethics Committee (2nd Floor, Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, UK; Tel: +44 (0)131 465 5680; Email: manx.neill@nhslothian.scot.nhs.uk), REC ref: 18/SS/0055, IRAS project ID: 239109
2. Approved 26/07/2019, North East- Newcastle & North Tyneside 1 Research Ethics Committee (HRA Newcastle, Newcastle Blood Donor Centre, Holland Drive, Newcastle Upon Tyne, NE2 4NQ; Tel: +44 (0)207 1048084; Email: nrescommittee.northeast-newcastleandnorthtyneside1@nhs.net), REC ref: 18/NE/0150, IRAS project number: 244590

Study design

Prospective multicentre observational longitudinal study

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format

Condition

Stroke

Intervention

Baseline assessment will record demographic, clinical, family history, education, socioeconomic, lifestyle and prestroke functioning (mRS), including non-testability in patients without capacity. Lab data (including BP, carotid Doppler, ECG, echocardiography where performed) will also be collected. Initial direct-to-patient cognitive assessment will use brief cognitive screening tools including delirium, fatigue, mood, apathy, and frailty. Informants will be asked about prestroke cognition. Routine bran imaging (CT or MRI) will be collected to classify the index stroke and pre stroke findings with standard tools. Bloods will be taken for analysis of genetics.

Early follow up will be at 4-8 weeks post baseline assessment. Here the researchers will also assess cognition, fatigue, mood, apathy and health-related quality of life. Bloods will be taken for analysis of inflammatory markers and stored for future analysis. The researchers will also record if the patient has died or changed their place of residence.

Annual follow-up will be conducted for a minimum of 2 years, maximum of four years by post or phone, using validated functional (mRS), recurrent vascular events, cognition, mood, apathy, fatigue, health-related quality of life assessments as above, from both participant and informant.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Rates of cognitive impairment and dementia up to at least two years after stroke, measured using a seven-level ordered categorical scale compromising cognition (normal, impairment in one domain, impairment in two or more domains), dementia (mild, moderate, severe) and death. The outcome scale is driven by information from the Montreal Cognitive Assessment (MoCA), the Modified Telephone Interview for Cognitive Status (TICS-m), Modified Rankin Scale (MRS), Barthel Index, IQCODE, disposition (need for nursing care), and evidence of dementia (formal diagnosis, taking a cholinesterase inhibitor or memantine) or death. These outcomes are measured at baseline, 4-8 weeks, and annually for a minimum of 4 years.

Secondary outcome measures

Measured at baseline, 4-8 weeks and annually for a minimum of 2 years, maximum of 4 years:
1. Cognition is measured using; presence of memory of thinking problems: single question yes/no, Verbal Fluency phonemic (letter F, A, S, Montreal Cognition Assessment (MoCA), Trail Making A & B, Telephone Interview of Cognition Scale- modified (TICS-m), Letter digit coding, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Boston naming test (BNT) and a clinical diagnosis of dementia (e.g. from a memory clinic)
2. Mood is measured using; Patient health questionnaire (PHQ-9 and PHQ-SADS); Generalised Anxiety Disorder (GAD), Zung depression scale (ZDS), Office National Statistics-4 (ONS-4) and a clinical diagnosis of depression

Overall trial start date

01/07/2018

Overall trial end date

30/06/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients aged 18 and over
2. No upper age limit
3. No severity limit
4. Ischaemic or spontaneous haemorrhagic (non-traumatic, non-subarachnoid haemorrhage, non-AVM) stroke and transient ischaemic attack (TIA)
5. Expected to survive at least 12 weeks

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2000

Participant exclusion criteria

1. Inclusion criteria not met
2. Aneurysmal, traumatic or AVM-associated haemorrhage or subarachnoid haemorrhage
3. Stroke mimics such as brain tumours
4. Prior diagnosis of cognitive impairment or dementia is NOT an exclusion criteria

Recruitment start date

25/09/2018

Recruitment end date

25/09/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Clinical Brain Sciences
Chancellor's Building Little France Crescent
Edinburgh
EH16 4SB
United Kingdom

Trial participating centre

NHS Greater Glasgow and Clyde
Glasgow Royal Infirmary 84 Castle Street
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Nottingham City Hospital Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Salford Royal NHS Trust
Salford Royal Hospital Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

University College London Hospitals NHS Trust
University College Hospital 235 Euston Road Fitzrovia
London
NW1 2BU
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Trust
Cambridge Biomedical Campus Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

University Hospitals Leicester NHS Trust
Leicester Royal Infirmary Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Lancashire Teaching Hospital NHS Trust
Royal Preston Hospital Sharoe Green Lane Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

Kings College Hospital NHS Trust
Kings College Hospital Denmark Hill Brixton
London
SE5 9RS
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Trust
Horton General Hospital Oxford Road
Oxford
OX16 9AL
United Kingdom

Sponsor information

Organisation

Academic and Clinical Central Office for Research and Development (ACCORD)

Sponsor details

University of Edinburgh & NHS Lothian
ACCORD
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
+44 (0)131 242 3326
resgov@accord.scot

Sponsor type

Hospital/treatment centre

Website

www.accord.ed.ac.uk

Funders

Funder type

Charity

Funder name

Stroke Association

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Funder name

Alzheimer's Society

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Funder name

British Heart Foundation

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Prior to the presentation of the primary results, the statistical analysis plan will be published. Protocol paper is in preparation. Study materials can be accessed via the website or on contacting Dr Rosalind Brown (Rosalind.Brown@ed.ac.uk). Planned publication of the results in peer-reviewed journals and presentations at national and international conferences.

IPD sharing statement
The anonymised study data will be made available for use by external investigators in appropriate analyses upon request via a publicly accessible portal (e.g. University of Edinburgh datashare https://datashare.is.ed.ac.uk/). Data from R4VaD will also be shared with individual patient data pooling projects involving stroke and dementia (e.g. Virtual International Stroke Trials archive-Cognition, VISTA-COG; Virtual International Cardiovascular and Cognitive Trials Archive, VICCTA, http://www.virtualtrialsarchives.org; and STROKOG https://cheba.unsw.edu.au/consortia/strokog; Dementia Platform UK Portal https://portal.dementiaplatform.uk). Similarly, anonymised baseline and on-treatment neuroimaging data will be published. The mechanisms and processes for managing external access will be determined during the course of the study.

Intention to publish date

30/06/2024

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

25/07/2019: Trial's existence confirmed by ethics committee.