Condition category
Circulatory System
Date applied
28/06/2018
Date assigned
08/08/2018
Last edited
17/04/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Cognitive impairment is common after cardiac (heart) surgery, particularly in older people. Up to six in every 10 patients who undergo cardiac surgery have some degree of cognitive impairment six months after their surgery. The mechanisms involved are unclear. Recent research in brain imaging has identified some regions of the brain involved in learning and memory which are working when the brain is “at rest”, that is when the subject is not performing an explicit cognitive task. These brain networks, so called “resting state networks”, represent the baseline, or default, mode of the brain. Brain imaging studies have shown that when the activity of resting state networks is reduced, patients are more likely to develop cognitive impairment. There is currently limited evidence to suggest whether cardiac surgery causes damage to resting state networks thus leading to cognitive impairment. This study will investigate changes in resting state networks in 20 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) using functional brain magnetic resonance imaging (fMRI). This study will help doctors to better understand the mechanisms leading to cognitive impairment following cardiac surgery and will aid in the development of preventive strategies and new treatments.

Who can participate?
Patients aged between 60 and 75 undergoing coronary artery bypass surgery (CABG) with CPB at the Bristol Heart Institute

What does the study involve?
All patients undergo two fMRI scans and cognitive assessments. The first scan and cognitive assessments take place around 1 week before their heart surgery and the second around 6 weeks after surgery. Each fMRI scan takes about 40 minutes. The cognitive tests take around 45 minutes and assess memory, coordination and levels of attention.

What are the possible benefits and risks of participating?
There are no direct benefits of participating in this study. This study of the potential role of default mode networks in CPB-related cognitive decline could aid the development of interventions to improve neurocognitive outcomes following surgery, such as cognitive training and physical exercise. There are no associated risks with functional MRI or the neurocognitive assessments.

Where is the study run from?
University Hospitals Bristol NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
April 2018 to March 2020

Who is funding the study?
Above and Beyond (UK)

Who is the main contact?
Lucy Ellis
codec-study@bristol.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Lucy Ellis

ORCID ID

Contact details

Clinical Trials and Evaluation Unit
Bristol Royal Infirmary
Level 7
Marlborough Street
Bristol
BS2 8HW
United Kingdom
+44 (0)117 342 2374
codec-study@bristol.ac.uk

Type

Scientific

Additional contact

Dr Maria Pufulete

ORCID ID

Contact details

Clinical Trials and Evaluation Unit
Bristol Royal Infirmary
Level 7
Marlborough Street
Bristol
BS2 8HW
United Kingdom
+44 (0)117 342 2526
codec-study@bristol.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Investigation of neural mechanisms of COgnitive DEcline after Cardiac surgery with resting state fMRI (CODEC): a pilot study

Acronym

CODEC

Study hypothesis

The primary hypothesis is that default mode network connectivity is impaired following coronary artery bypass graft surgery with cardiopulmonary bypass and correlates with neurocognitive testing.

Ethics approval

South West – Central Bristol Research Ethics Committee - submission pending

Study design

Single-centre observational study

Primary study design

Observational

Secondary study design

Trial setting

Hospitals

Trial type

Other

Patient information sheet

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

Condition

Cardiac disease/coronary artery bypass grafting

Intervention

Patients who consent will be required to undergo two functional MRI scans and neuro-cognitive assessments. Patients will have the first scan and neuro-cognitive assessments pre-surgery (1- 8 weeks before surgery date). The second scan and assessments will take place post-surgery (5-10 weeks post surgery date). Each fMRI scan will take approximately 40 minutes. The scans will take place at the Bristol Clinical Research and Imaging Centre. The neuro-cognitive assessment involves tests that assess memory, coordination and levels of attention. As part of the assessment patients will also complete two questionnaires examining current mood/emotional state. Each neuro-cognitive assessment will take approximately 45 minutes.

Intervention type

Other

Phase

Drug names

Primary outcome measure

The change from baseline in default mode network connectivity in the brain post cardiac surgery as assessed by resting state fMRI performed 5-10 weeks post operatively

Secondary outcome measures

1. Change from baseline in cognitive ability as assessed by standard neurocognitive tests administered 5- 10 weeks post operatively
2. Length of intensive care unit (ICU)/high dependency unit (HDU) stay. This outcome is assessed during the patient’s hospital stay after their surgery.
3. All-cause mortality within 30 days of surgery
4. Clinical outcomes (assessed from surgery until follow up visit 5- 10 weeks post-surgery), defined as:
4.1. Infectious complications i.e. sepsis (defined antibiotic treatment for suspected infection, and the presence of SIRS1 within 24 hours prior to start of antibiotic treatment) or wound infection (ASEPSIS score >20; sternum, leg and arm (if applicable); wounds will be assessed at least once during a participant’s hospital stay
4.2. Stroke (validated by CT scanning); assessment of brain imaging (CT or MRI), in association with new onset focal or generalised neurological deficit (defined as deficit in motor, sensory or co-ordination functions)
4.3. ST elevation myocardial infarction accompanied by troponin > 5 ng / ml
4.4. Post-operative acute kidney injury (defined as AKIN criteria stage 1, 2 or 3)
4.5. Respiratory complications i.e. re-intubation, ventilation

The study will also assess the relationship between cognitive decline assessed by the neurocognitive tests (secondary outcome 1) and changes in resting state network connectivity assessed by fMRI (primary outcome).

Overall trial start date

30/04/2018

Overall trial end date

01/03/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged between 60-75 years
2. Electively referred for isolated coronary artery bypass grafting

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

20 participants

Participant exclusion criteria

1. Prisoners and adults lacking capacity to consent
2. Contraindications to MR (implanted electronic devices, metallic foreign bodies, claustrophobia, body weight >140 kg or waist perimeter exceeding manufacturer's recommendations and others according to manufacturer’s recommendations and generally accepted guidelines)
3. Patients with a neurological disorder (e.g. epilepsy, Alzheimer’s, dementia and Parkinson’s disease)
4. Patients with a diagnosed psychiatric disorder (e.g. schizophrenia, psychosis), drug or alcohol addiction
5. Patients with an already identified as having cognitive impairment (e.g. memory and/or attentional deficits) as defined by psychometric assessment or a preoperative Mini-mental State Examination score < 24. The Mini-mental State Examination will be adminstered after consent but prior to any of the cognitive assessements or fMRI scan
6. Patients who have previously sustained a stroke, intra-cerebral haemorrhage, acquired brain injury
7. Patients unable to complete the cognitive assessments required for the trial e.g. due to language difficulties, visual or hearing impairment

Recruitment start date

15/04/2019

Recruitment end date

15/12/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Marlborough Street
Bristol
BS1 3NU
United Kingdom

Sponsor information

Organisation

University Hospitals Bristol NHS Foundation Trust

Sponsor details

Research and Innovation
Level 3
Education Centre
Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Above and Beyond (Registered Charity Number: 229945)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The findings will be disseminated by usual academic channels, i.e. presentation at international meetings, as well as by peer-reviewed publications and through patient organisations and newsletters to patients, where available.

IPD sharing statement
Anonymised individual patient data (baseline, operative, outcome data and adverse events) will be made available for secondary research, conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the MRC Policy on Data Preservation and Sharing regarding scientific quality, ethical requirements and value for money. Please contact Prof. Chris Rogers (chris.rogers@bristol.ac.uk) to discuss any data requests. Data will be made after the study has been closed and the primary publication is out. It will be made available indefinitely. The patient information leaflet which participants consent to explains that data may be provided to researchers running other research studies.

Intention to publish date

30/10/2020

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

17/04/2019: The following changes were made to the trial record: 1. The recruitment start date was changed from 10/09/2018 to 15/04/2019. 2. The recruitment end date was changed from 10/06/2019 to 15/12/2019. 3. The overall trial end date was changed from 30/10/2019 to 01/03/2020.