Condition category
Circulatory System
Date applied
13/08/2018
Date assigned
24/09/2018
Last edited
06/08/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Suspended

Plain English Summary

Background and study aims
Stroke-associated infection (SAI) is one of the most common complications of stroke, affecting up to one third of patients, and is the biggest factor for predicting the likelihood of significant disability or death. Currently, there are no effective treatments that prevent SAI and improve stroke outcome. Current evidence has found that stroke can impair the body's natural ability to fight infection but the process has never been fully understood. Using laboratory models of stroke, researchers have investigated how having a stroke can affect the cells that make up the body's natural immune system. In healthy people, special immune cells called B cells help the body respond quickly to infection by triggering the production of antibodies, but after stroke this process is interrupted. The aim of this study is to measure to scale of B-cell changes after stroke, and assess the processes involved and the consequences of the changes.

Who can participate?
Patients aged 18 and over who have had a stroke and healthy volunteers

What does the study involve?
Blood samples are taken from stroke patients at 24-48 hours after their stroke began to measure the levels of B cells. Further assessments include alternate daily infection screen on days 1-7 after the stroke. A single blood sample is also taken from healthy volunteers of a similar age and sex.

What are the possible benefits and risks of participating?
There are no expected benefits except participants will be helping to increase the understanding of the impact of stroke on the function of the immune system. Risks include discomfort and bruising as a result of blood sampling, and data protection, as research staff will be required to access the medical notes of the patients and will be storing personal data for a short period of time.

Where is the study run from?
Salford Royal NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
August 2018 to May 2021

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Prof. Craig Smith
craig.smith-2@manchester.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Craig Smith

ORCID ID

http://orcid.org/0000-0002-9078-9919

Contact details

CSB
Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom
+44 (0)161 206 0623
craig.smith-2@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

237040

Study information

Scientific title

Understanding stroke-induced B cell changes and their relationships with stroke-associated infection

Acronym

Study hypothesis

Study rationale is to determine the effects of stroke on innate-like B cells (type of immune cell).

Ethics approval

NRES Committee North West, 18/07/2018, ref: 18/NW/0415

Study design

Single-centre prospective observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format. For participant information sheet (PIS), please contact Sharon.hulme@manchester.ac.uk

Condition

Acute stroke

Intervention

Baseline clinical characteristics performed following consent (including past medical history, prior level of independence, current stroke severity (NIHSS), risk factors and swallow status), current antibiotic treatment, standardised Stroke-Associated Infection (SAI) screen based on Centers for Disease Control and Prevention [CDC] criteria (including clinical features and most recent clinical, laboratory and other investigation findings).

Blood samples will be obtained from stroke patient participants at 24-48h post stroke onset and will be measured for B cell subset quantification by flow cytometry and for the isolation of B cells for ex vivo stimulation assays to measure functional responsiveness at the School of Biological Sciences, University of Manchester. In addition, a single blood sample will be obtained and analysed in the same way from non-stroke controls of a similar age and sex. Further research assessments including alternate daily infection screen (day 1-7 post stroke).

Differences in outcome measures between stroke patients and non-stroke controls will be compared using Student’s t test or non-parametric equivalent. Anonymised clinical data including incidence of SAI and clinical outcome assessment (telephone assessment of modified Rankin Scale score) will be correlated with concentrations of blood markers assessed by Pearson correlation or non-parametric equivalent.

Added 15/06/2020:
The COVID-19 sub-study will recruit patients with suspected or confirmed COVID-19 infection prior to stroke or complicating current stroke to investigate the effect of stroke on immune susceptibility to infection. Blood sampling at a single timepoint within 7 days of stroke onset will allow immunophenotyping analysis. Sub-study participants will remain in the trial for the same duration of participants in the main trial and undergo alternate daily follow-up during in-patient stay (to a maximum of 7 days from date/time of blood sampling) and telephone follow-up at 3 months to assess recovery using modified Rankin Scale score.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Numbers and composition of blood B cell subsets and key immune cell classes, measured using flow cytometry at 24-48h post stroke onset in stroke patients
2. Concentration of blood IgM and catecholamines (noradrenaline and adrenaline), measured using multiplex array, ELISA, EIA and HPLC (high-performance liquid chromatography) at 24-48h post stroke onset in stroke patients and in non-stroke controls
3. Functional responsiveness (e.g. antibody secretion) of blood B cells measured by ex vivo stimulation assay at 24-48h post stroke onset in stroke patients and in non-stroke controls

Added 15/06/2020:
4. Immunological characteristics/markers associated with vulnerability to COVID-19 (sub-study participants only) using multiplex array, ELISA, EIA and HPLC (high-performance liquid chromatography) within 7 days post-stroke onset

Secondary outcome measures

1. Incidence of Stroke-Associated Infection (SAI) based on Centers for Disease Control and Prevention [CDC] criteria at 3 months
2. Clinical outcome assessed with telephone assessment of modified Rankin Scale score at 3 months

Overall trial start date

06/08/2018

Overall trial end date

01/05/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Stroke patients:
1. Age ≥18 years
2. Clinical diagnosis of middle cerebral artery (MCA) territory ischaemic stroke or haemorrhage stroke (primary intracerebral haemorrhage)
3. NIHSS ≥8
4. Swallowing difficulties identified on swallow screen performed within 24h of stroke admission
5. Capacity to give consent to blood sampling and follow-up OR availability of personal/professional consultee
6. Blood draw can be undertaken 24-48h after stroke onset (or time last seen well)

Non-stroke controls:
Aged over 18

Added 15/06/2020:
COVID-19 sub-study:
1. Age ≥18
2. Clinical diagnosis ischaemic stroke or haemorrhagic stroke (primary intracerebral haemorrhage; ICH) in any cerebral territory
3. Suspected or confirmed diagnosis of COVID-19 (either prior to stroke admission or within 7 days of stroke onset)*
4. NIHSS >2 (regardless of swallow status)
5. Capacity to give consent to participation or verbal declaration from personal consultee prior to blood sampling
6. Blood draw can be undertaken within 7 days of stroke onset (or time last seen well)

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

80 stroke participants, 50 non-stroke control participants, 10-15 COVID-19 sub-study participants

Participant exclusion criteria

Stroke patients:
1. Stroke of other aetiology or unclear diagnosis (e.g. traumatic, stroke mimic)
2. Rapidly improving symptoms at the point of screening
3. History of infection treated with antibiotics at admission or in the preceding 6 weeks
4. Unlikely to survive or palliative care considered to be imminent

Non-stroke controls:
1. Previous stroke
2. Infection or antibiotic therapy in previous 6 weeks

Added 15/06/2020:
COVID-19 sub-study:
1. Stroke of other aetiology or unclear diagnosis (e.g. traumatic, stroke mimic)
2. Rapidly improving symptoms at the point of screening
3. Unlikely to survive or palliative care considered to be imminent

Recruitment start date

06/08/2018

Recruitment end date

31/07/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Sponsor information

Organisation

Salford Royal NHS Foundation Trust

Sponsor details

Summerfield House
544 Eccles New Road
Salford
M5 5AP
United Kingdom
+44 (0)161 206 7050
beverley.greenahlgh@srft.nhs.uk

Sponsor type

Hospital/treatment centre

Website

https://www.ncaresearch.org.uk/

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

A manuscript of study results will be submitted to peer review journal and presented at national conference (UK Stroke Forum). In addition, a lay summary for participants/personal consultees will be made available via Salford Citizen Scientist or Salford R&D forum.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Craig Smith (craig.smith-2@manchester.ac.uk). Consent will be sought from all participants, data is fully anonymised.

Intention to publish date

30/11/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/08/2020: The intention to publish date was changed from 30/06/2021 to 30/11/2021. 15/06/2020: The following changes were made to the trial record: 1. The interventions, primary outcome measures, inclusion and exclusion criteria were updated. 2. The target number of participants was changed from '80 stroke participants, 50 non-stroke control participants' to '80 stroke participants, 50 non-stroke control participants, 10-15 COVID-19 sub-study participants'. 12/06/2020: Contact details updated. The overall trial end date was changed from 30/11/2020 to 01/05/2021. 27/04/2020: Due to current public health guidance, recruitment for this study has been paused as of 23/03/2020.