Perioperative Research Into Memory: Cognitive Outcome Following Major Burns

Completed

• Conditions: Major Injury
• Interventions: Behavioral: Face-to-face neurocognitive tests; Behavioral: Psychological screening; Other: fMRI; Behavioral: Quality of Life Self-Assessment data

• Registration Number: NCT03470844
• Lead Sponsor: Chelsea and Westminster NHS Foundation Trust

Brief Summary

The long term survival of patients who require admission to critical care (CC) following a major burn injury (MBI) continues to improve with advanced clinical management. There has been increasing interest into cognitive dysfunction (CD) due to neuroinflammation (NI) following CC, anaesthesia, surgery, and the association of NI with diseases characterised by CD such as Alzheimer's disease. Patients who suffer a MBI and who subsequently require admission to CC will be at uniquely high risk for CD. MBI produces an exaggerated and prolonged systemic inflammatory response, with NI demonstrated in animal models. Additionally NI can be exaggerated by insults such as sepsis, anaesthesia, and surgical trauma, common and often necessary following MBI. The aim of this study is to identify CD using cognitive tests to examine for deficits in working memory and executive function. Test proposed to use are the Hopkins Verbal Learning and Verbal Fluency tests, and a validated computerised battery (CogState). Neuroinflammation and underlying pathophysiology using fMRI and spectroscopy, known to demonstrate biomarkers for CD and NI. QoL will be assessed using the validated EQ-5D tool.

The Inclusion criteria; patients who survive their burns injury (greater than 15% total body surface area) and require mechanical ventilation. Primary exclusion criteria; admission with toxic epidermal necrolysis syndrome, and evidence of head trauma.

Detailed Description

This is a novel, proof of principle, prospective, cohort design, observational clinical study to assess for functional brain reorganisation, structural changes and long-term cognitive dysfunction following major burns injury and intensive care admission. The hypothesis is that following a major burns injury and intensive care admission patients will have neurocognitive dysfunction and demonstrable functional alterations seen on functional MRI due to neuroinflammation as a result of the primary injury and subsequent inflammatory insults.

Study Timeline

• Study Start: 2015-08-05
• Primary Completion: 2016-04-30
• Study First Submitted: 2016-05-10
• Study Completion: 2017-10-30
• Status Verified: 2018-03
• Study First Submitted QC: 2018-03-19
• Last Update Submitted: 2018-03-19
• Study First Posted: 2018-03-20
• Last Update Posted: 2018-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Survival following admission to Chelsea and Westminster Burns Intensive Care Unit between 2004-2013 with a burn injury > 15% total body surface area, requiring intubation and ventilation

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Exclusion Criteria

• Patients under 16.
• Patients with toxic epidermal necrolysis syndrome or evidence of head trauma.
• Patients with evidence of risk to psychological safety from inclusion in study: any patient currently held under section of the Mental Health Act, any patient receiving formal psychiatric treatment (including involvement in a Personality Disorder Unit, being under voluntary section, current re-occurrence of chronic self harm), any patient currently detained at her Majesty's pleasure, any current substance abuse, or at the discretion of professional opinion following historical assessment of notes. - Patients with contraindications to MRI (patients with non-compatible pacemakers, patients with metallic foreign bodies e.g. metal sliver in their eye, patients with non-compatible surgical metal work, patients with severe claustrophobia).
• Patient refusal or inability to give full informed consent.
• Patients unable to understand plain verbal or written English.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
5-10 years post severe burn injury	Face-to-face neurocognitive tests	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
5-10 years post severe burn injury	Psychological screening	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
5-10 years post severe burn injury	Quality of Life Self-Assessment data	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
2-5 years post severe burn injury	Psychological screening	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
2-5 years post severe burn injury	Face-to-face neurocognitive tests	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
2-5 years post severe burn injury	Quality of Life Self-Assessment data	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
1-2 years post severe burn injury	Face-to-face neurocognitive tests	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
1-2 years post severe burn injury	Psychological screening	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
5-10 years post severe burn injury	fMRI	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
Control	Quality of Life Self-Assessment data	Healthy age, gender, socioeconomic and educational level matched control. Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
2-5 years post severe burn injury	fMRI	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
1-2 years post severe burn injury	fMRI	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
Control	Face-to-face neurocognitive tests	Healthy age, gender, socioeconomic and educational level matched control. Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
1-2 years post severe burn injury	Quality of Life Self-Assessment data	Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
Control	Psychological screening	Healthy age, gender, socioeconomic and educational level matched control. Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.
Control	fMRI	Healthy age, gender, socioeconomic and educational level matched control. Interventions: * Face-to-face neurocognitive tests examining attention, processing speed, working memory and executive function. * Psychological screening for the symptoms of depression, anxiety and post-traumatic stress disorder using the patient health questionnaire (PHQ9), generalised anxiety (GAD7) scoring systems and the trauma screening questionnaire. * fMRI studies including resting state fMRI, T1w-mpr, T2w-FLAIR, Diffusion Tensor Imaging (DTI) with 30 directions, Spectroscopy CSI chemical shift imaging, Spectroscopy SVS single voxel, susceptibility weighted imaging (SWI), double inversion recovery (DIR) and Perfusion ASL. * Quality of Life Self-Assessment data.

Primary Outcome Measures

Name	Time	Method
Neurocognitive function	5 years	Specifically to investigate cognitive tasks using a battery of computerised tests.

Secondary Outcome Measures

Name	Time	Method
Neuroinflammatory changes analysis.	5 years	Functional MRI scan

Trial Locations

Locations (1)

The Burn Intensive Care Unit (BICU), Chelsea and Westminster Hospital; 🇬🇧 London, United Kingdom