Clinical trial NCT03242395: PRIME: Cognitive Outcome Following Major Burns
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cognitive Dysfunction
Burns
Inflammation, Brain
Quality of Life
Anxiety
Depression
PostTraumatic Stress Disorder
Keywords: Neuroinflammation
fMRI
Post-operative cognitive dysfunction
Systemic inflammation
Severe burns
Lead sponsor: Chelsea and Westminster NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Westminster
name: Imperial College Healthcare NHS Trust
name: Imperial College London
First posted: 2017-08-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Severe burns survivors

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurocognitive deficit
timeFrame: Within 10 years of injury
Secondary outcomes:
measure: Quality of Life
timeFrame: Within 10 years of injury
measure: Neuroinflammation
timeFrame: Within 10 years of injury
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Foundation Trust
Study officials:
affiliation: Anaesthetic and Intensive Care Consultant
name: Marcela P Vizcaychipi, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: