Condition category
Mental and Behavioural Disorders
Date applied
21/11/2016
Date assigned
11/05/2017
Last edited
28/03/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Dementia is an umbrella term used to refer to a wide range of symptoms linked to with a reduction in memory and/or other thinking skills which reduce a person's ability to perform everyday activities. Inflammation is generally a beneficial response to tissue damage or infection. However, when inflammation is extensive or prolonged this can damage healthy tissues and disrupt normal cellular function. Research suggests that acute illnesses or injury causing inflammation can accelerate dementia. However there are few studies which examine underlying mechanisms of how this happens in humans. This study aims to address this gap. The study will compare markers of inflammation and injury found in the blood and cerebrospinal fluid (fluid which bathes the spinal cord (CSF)) of people with and without confirmed dementia who fracture their fracture. A hip fracture is a common example of an acute injury causing an inflammatory response. People who fracture their hip will undergo an operation to repair it. A common procedure during this operation is the giving of spinal aesthetic. This involves inserting a needle into the patient’s spinal space and injecting anaesthesia into CSF. This means CSF can be collected before operation via the same needle.

Who can participate?
Patients due to have a hip fracture operation via spinal anaesthesia with all levels of pre-operative confusion.

What does the study involve?
Patients are allocated to one of three groups after their operation: those with confirmed dementia (as obtained from patient’s GP notes/hospital records and/or carer insight), non-dementia (no evidence of dementia found in patent’s GP notes/medical records) groupings; and pre-operatively confused but without confirmed dementia. Consent is gained for the storage of surplus samples in a bio-bank to help future studies. Pre-operative blood and CSF samples, post-operative blood samples and a short cognitive questionnaire is administered to all patients.

What are the possible benefits and risks of participating?
For patients and their families there are no direct benefits taking part. However it is hoped that the research may help similar patient groups in the future. Postdural-puncture headaches (PDPH) are a common side-effect of spinal anaesthesia. The collection of CSF may slightly increase the chance of PDPH.

Where is the study run from?
This study is being run by University of East Anglia (UK) and takes place in hospitals in the UK.

When is the study starting and how long is it expected to run for?
November 2016 to November 2018

Who is funding the study?
Alzheimer’s Research UK (UK)

Who is the main contact?
Dr Simon Hammond
s.hammond@uea.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Simon Hammond

ORCID ID

http://orcid.org/0000-0002-0473-3610

Contact details

Norwich Medical School
University of East Anglia
Norwich Research Park
Norwich
NR4 7TJ
United Kingdom
+44 1603 591460
s.hammond@uea.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

1

Study information

Scientific title

ASCRIBED: The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients

Acronym

ASCRIBED

Study hypothesis

The aim of this study is to evaluate whether hip fracture patients with dementia show elevated markers of systemic inflammation and of brain inflammation in comparison to stable patients with dementia and hip fracture patients without dementia, as measured by biomarkers in cerebrospinal fluid (CSF) and blood.

Ethics approval

NRES Committee North East - Newcastle & North Tyneside 1, 24/03/2017, ref: ISRCTN43803769

Study design

Observational case-control study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Dementia patients admitted to acute hospital settings with a hip fracture.

Intervention

Participants due to have a hip fracture operation via spinal anaesthesia with all levels of pre-operative confusion (as assessed by clinical screening procedures, AMTS (England) and 4AT (Scotland)) will be approached and recruited. Capacity will be assessed and consent or consultee agreement gained. During pre-operative procedures a blood sample will be taken and cerebrospinal fluid (CSF) collected.

48 hours post-operatively patients will be approached to undertake a short cognitive test and have a second blood sample collected. A suitable informant will also be sought to complete a proxy measure about the patient’s memory and thinking. At 1 month post-operatively patient's GP and medical records will be accessed to search for evidence of dementia. Patients also taking part in ASCRIBED’s sister study PERFECTED (ISRCTN99336264) will be asked to give blood samples at 1, 3 and 6 months post-operatively.

Intervention type

Other

Phase

Drug names

Primary outcome measures

CSF inflammation and injury is measured by TNF-α, IL-1RA, IL-1β, IL-6 and Neurogranin, tTau, Synaptotagmin, SNAP-25 at baseline.

Secondary outcome measures

Magnitude of the brain inflammation is measured by brain injury markers (phospho-Tau, NFL, neurogranin, synaptotagmin, SNAP-25) in CSF at baseline.

Exploratory:
1. Higher levels of inflammatory and brain injury markers in CSF and blood are associated with worsening cognitive and functional decline measured by MMSE at 6 months post-operatively
2. Cytokines ratio CSF:blood pre-op time will show higher ratios in dementia than non-dementia patients measures in blood and CSF at baseline

Overall trial start date

01/11/2016

Overall trial end date

01/11/2018

Reason abandoned

Eligibility

Participant inclusion criteria

Group 1: Pre-operative acute hip fracture patients with confusion as defined by the Abbreviated Mental Test (England) or 4AT (Scotland):
Inclusion Criteria:
1. Patient must have had a confirmed proximal hip fracture requiring an operation and be aged 60 or older at the time of operation
2. Patient has a pre-operative Abbreviated Mental Test score of 8 or below or 4AT score of 1 or above
3. Patient must be undergoing spinal anaesthesia

Group 2: Pre-operative acute hip fracture patients without confusion as defined by the Abbreviated Mental Test (England) or 4AT (Scotland):
Inclusion Criteria:
1. Patient must have had a confirmed proximal hip fracture requiring an operation and be aged 60 or older at the time of operation
2. Pre-operative Abbreviated Mental Test score of 9 or above or 4AT score of 0
3. Patient must be undergoing spinal anaesthesia

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

400

Participant exclusion criteria

Group 1 and 2:
1. Decision taken not to have hip surgery
2. Patient has head trauma with bleeding as indicated by a CT scan
3. Patient has confirmed diagnosis of Parkinson’s disease
4. Patient not expected to survive beyond 4 weeks

Recruitment start date

01/06/2017

Recruitment end date

31/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Princess Royal University Hospital
Farnborough Common
Orpington
BR6 8ND
United Kingdom

Trial participating centre

Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Pinderfields Hospital
Mid Yorkshire Hospitals NHS Trust
Wakefield
-
United Kingdom

Trial participating centre

York Teaching Hospital NHS Foundation Trust
York
-
United Kingdom

Trial participating centre

Princess Royal Hospital, Brighton & Sussex University Hospitals NHS Trust
-
-
United Kingdom

Trial participating centre

James Paget University Hospital
Great Yarmouth
-
United Kingdom

Trial participating centre

Russells Hall Hospital
The Dudley Group NHS Foundation Trust
Dudley
-
United Kingdom

Trial participating centre

Peterborough City Hospital
North West Anglia NHS Foundation Trust
Peterborough
-
United Kingdom

Trial participating centre

Queen’s Medical Centre Campus
Nottingham University Hospitals NHS Trust
Nottingham
-
United Kingdom

Trial participating centre

Royal Blackburn Hospital
East Lancashire Hospitals NHS Trust
Blackburn
-
United Kingdom

Trial participating centre

University Hospital of North Tees
North Tees and Hartlepool NHS Foundation Trust
Stockton-on-Tees
-
United Kingdom

Trial participating centre

The Royal Shrewsbury Hospital
The Shrewsbury and Telford Hospital NHS Trust
Shrewsbury
-
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust
Doncaster
-
United Kingdom

Trial participating centre

Royal United Hospital Bath NHS Foundation Trust
Bath
-
United Kingdom

Trial participating centre

University Hospital of North Durham
County Durham and Darlington NHS Foundation Trust
Durham
-
United Kingdom

Trial participating centre

Royal Bolton Hospital
Bolton NHS Foundation Trust
Bolton
-
United Kingdom

Trial participating centre

Kingston Hospital
Kingston Hospital NHS Foundation Trust
Kingston
-
United Kingdom

Trial participating centre

Royal Stoke University Hospital
University Hospitals of North Midlands NHS Trust
Stoke-on-Trent
-
United Kingdom

Trial participating centre

Countess of Chester Hospital NHS Foundation Trust
Chester
-
United Kingdom

Trial participating centre

Western Sussex Hospitals NHS Foundation Trust
-
-
United Kingdom

Trial participating centre

Medway Maritime Hospital
Medway NHS Foundation Trust
Gillingham
-
United Kingdom

Trial participating centre

Whiston Hospital
St Helens & Knowsley Teaching Hospitals NHS Trust
Rainhill
-
United Kingdom

Trial participating centre

Southampton General Hospital
University Hospital Southampton NHS Foundation Trust
Southampton
-
United Kingdom

Trial participating centre

Royal Devon & Exeter Hospital
Royal Devon and Exeter NHS Foundation Trust
Wonford
-
United Kingdom

Trial participating centre

Southend University Hospital NHS Foundation Trust
-
Southend-on-Sea
-
United Kingdom

Trial participating centre

The Ipswich Hospital NHS Trust
Ipswich
-
United Kingdom

Trial participating centre

The Princess Alexandra Hospital NHS Trust
Harlow
-
United Kingdom

Sponsor information

Organisation

University of East Anglia

Sponsor details

University of East Anglia
Norwich Research Park
Norwich.
NR4 7TJ
United Kingdom
+44 1603 591460
t.moulton@uea.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Alzheimer’s Research UK

Alternative name(s)

ARUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof Chris Fox, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, United Kingdom.

Intention to publish date

01/11/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

28/03/2018: Ethics approval details were added. 26/03/2018: The following changes were made: 1. Recruitment end date was changed from 28/02/2018 to 31/10/2018 2. Overall trial end date was changed from 31/08/2018 to 01/11/2018. 3. Intention to publish date was changed from 28/02/2019 to 01/11/2019. 22/02/2018: The plain English summary has been updated to reflect the updates in the study record. 20/02/2018: The overall trial end date has been updated from 28/02/2018 to 31/08/2018. The following sites were added: Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust, York Teaching Hospital NHS Foundation Trust, Princess Royal Hospital, Brighton & Sussex University Hospitals NHS Trust, James Paget University Hospital, Russells Hall Hospital, The Dudley Group NHS Foundation Trust, Peterborough City Hospital, North West Anglia NHS Foundation Trust, Queen’s Medical Centre Campus, Nottingham University Hospitals NHS Trust, Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, University Hospital of North Tees, North Tees and Hartlepool NHS Foundation Trust, The Royal Shrewsbury Hospital, The Shrewsbury and Telford Hospital NHS Trust, Doncaster Royal Infirmary, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Royal United Hospital Bath NHS Foundation Trust, University Hospital of North Durham, County Durham and Darlington NHS Foundation Trust, Royal Bolton Hospital, Bolton NHS Foundation Trust, Kingston Hospital, Kingston Hospital NHS Foundation Trust, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Countess of Chester Hospital NHS Foundation Trust, Western Sussex Hospitals NHS Foundation Trust, Medway Maritime Hospital, Medway NHS Foundation Trust, Whiston Hospital, St Helens & Knowsley Teaching Hospitals NHS Trust, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Royal Devon & Exeter Hospital (Wonford), Royal Devon and Exeter NHS Foundation Trust, Southend University Hospital NHS Foundation Trust, The Ipswich Hospital NHS Trust, and The Princess Alexandra Hospital NHS Trust 23/10/2017: Internal review.