PRIME: Cognitive Outcome Following Major Burns (PRIME)

Perioperative Research Into Memory (PRiMe): The Use of fMRI to Investigate Neuroinflammation, Cognitive Dysfunction and Quality of Life Following a Major Burn Injury and Critical Care Admission

PRIME aims to demonstrate through neurocognitive assessment that BICU patients will have a degree of neurocognitive dysfunction following a major burn, that this neurocognitive dysfunction is due to an underlying neuroinflammatory process by fMRI neuroimaging techniques, and that the neurocognitive deficit is associated with a reduced quality of life.

Study Overview

• Status: Completed
• Conditions: Depression; Quality of Life; Burns; Cognitive Dysfunction; Anxiety; PostTraumatic Stress Disorder; Inflammation, Brain

Detailed Description

Patients were matched with for age, sex and IQ (as determined by National Adult Reading Test scores) controlled volunteers.

Participants were assessed for the following domains: verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed. The domains were assessed with the following validated cognitive tests: The Hopkins Verbal Learning Test, Trail making parts A and B, phonemic, semantic and switching verbal fluency as well as the Cogstate computerised battery: Identification speed, Detection speed, One Card Learning accuracy, One Back test accuracy, Two Back test accuracy, International Shopping List total correct answers and Groton Maze Learning total errors. Evidence of neuroinflammation was assessed using an fMRI protocol (Resting state MRI, T1w-MPR, T2 Space, Diffusion Tensor Imaging with 30 directions, right frontal white matter and posterior cingulate gyrus Single Voxel Spectroscopy, and patient group Susceptibility Weighted Imaging.

Quality of life was measured using the EuroQoL 5 Dimensions and visual analogue scale. Independent Activities of Daily Living was also assessed. Mental Health (as a confounder) was measured using the Patient Health Questionnaire 9, the Beck Depression Index II, the Beck Anxiety Inventory and the Trauma Screening Questionnaire.

Statistical methods include significant differences between the patient and control group using the Student t test (parametric data), the Mann Witney U test (non parametric data) or the Fisher's Exact test (qualitative scoring systems). MELODIC in FSL software was used to decompose the rs-fMRI data into brain networks using independent component analysis (ICA) and connectivity in these networks patients and controls was compared using dual regression. FreeSurfer was used to extract brain regions from T1 images and compare the normalised volume of the hippocampus, amygdala and precuneus for patients and controls. DTI data were analysed using tract based spatial statistics (TBSS) in FSL and using FreeSurfer regions for the hippocampus, amygdala and precuneus. Cho/Cr, Cho/NAA and Ins/Cr ratios were extracted from MRS data using Tarquin. SWI images were reviewed for the presence of microbleeds by two Radiologists.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Severe burns survivors

Description

Inclusion Criteria:

• Invasive ventilation on a Burns Intensive Care Unit (BICU) within the previous ten years
• Burn injuries greater than 15% total body surface area (TBSA)
• Adult

Exclusion Criteria:

• Admission to BICU for other illnesses that were not burn related (such as Toxic Epidermal Necrolysis Syndrome)
• Evidence of head trauma
• Known substance misuse or alcohol excess
• Inability to understand plain verbal or written English
• Severe mental health issues
• Receiving formal psychiatric treatment
• Currently held under the Mental Health Act
• If the subject's psychological health was deemed to be at risk from inclusion
• Imprisoned
• Contraindications to MRI
• non-compatible pacemakers
• surgical metalwork or foreign bodies
• severe claustrophobia

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Burn patients; Adult survivors of severe burns who have been admitted to Burns ITU for invasive ventilation within 10 years of neurocognitive assessment
Controls; Healthy volunteers, controlled for age/sex/IQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive deficit	Median T score of cognitive results (verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed)	Within 10 years of injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	EuroQoL 5D score	Within 10 years of injury
Neuroinflammation	As per the functional Magnetic Resonance Imaging protocol	Within 10 years of injury

Collaborators and Investigators

• Sponsor: Chelsea and Westminster NHS Foundation Trust
• Collaborators: Imperial College London; Imperial College Healthcare NHS Trust; University of Westminster
• Investigators: Principal Investigator: Marcela P Vizcaychipi, MD PhD, Anaesthetic and Intensive Care Consultant

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): April 1, 2017

Study Registration Dates

• First Submitted: April 21, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (ACTUAL): August 8, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 8, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Neuroinflammation; fMRI; Systemic inflammation; Post-operative cognitive dysfunction; Severe burns
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurocognitive Disorders; Trauma and Stressor Related Disorders; Cognition Disorders; Stress Disorders, Traumatic; Burns; Encephalitis; Inflammation; Stress Disorders, Post-Traumatic; Cognitive Dysfunction
• Other Study ID Numbers: 14/LO/0049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO