<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03242395</url>
  </required_header>
  <id_info>
    <org_study_id>14/LO/0049</org_study_id>
    <nct_id>NCT03242395</nct_id>
  </id_info>
  <brief_title>PRIME: Cognitive Outcome Following Major Burns</brief_title>
  <acronym>PRIME</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chelsea and Westminster NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Westminster</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College Healthcare NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chelsea and Westminster NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PRIME aims to demonstrate through neurocognitive assessment that BICU patients will have a&#xD;
      degree of neurocognitive dysfunction following a major burn, that this neurocognitive&#xD;
      dysfunction is due to an underlying neuroinflammatory process by fMRI neuroimaging&#xD;
      techniques, and that the neurocognitive deficit is associated with a reduced quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients were matched with for age, sex and IQ (as determined by National Adult Reading Test&#xD;
      scores) controlled volunteers.&#xD;
&#xD;
      Participants were assessed for the following domains: verbal ability, verbal and visual&#xD;
      learning, short-term memory, working memory, executive function, attention and processing&#xD;
      speed. The domains were assessed with the following validated cognitive tests: The Hopkins&#xD;
      Verbal Learning Test, Trail making parts A and B, phonemic, semantic and switching verbal&#xD;
      fluency as well as the Cogstate computerised battery: Identification speed, Detection speed,&#xD;
      One Card Learning accuracy, One Back test accuracy, Two Back test accuracy, International&#xD;
      Shopping List total correct answers and Groton Maze Learning total errors. Evidence of&#xD;
      neuroinflammation was assessed using an fMRI protocol (Resting state MRI, T1w-MPR, T2 Space,&#xD;
      Diffusion Tensor Imaging with 30 directions, right frontal white matter and posterior&#xD;
      cingulate gyrus Single Voxel Spectroscopy, and patient group Susceptibility Weighted Imaging.&#xD;
&#xD;
      Quality of life was measured using the EuroQoL 5 Dimensions and visual analogue scale.&#xD;
      Independent Activities of Daily Living was also assessed. Mental Health (as a confounder) was&#xD;
      measured using the Patient Health Questionnaire 9, the Beck Depression Index II, the Beck&#xD;
      Anxiety Inventory and the Trauma Screening Questionnaire.&#xD;
&#xD;
      Statistical methods include significant differences between the patient and control group&#xD;
      using the Student t test (parametric data), the Mann Witney U test (non parametric data) or&#xD;
      the Fisher's Exact test (qualitative scoring systems). MELODIC in FSL software was used to&#xD;
      decompose the rs-fMRI data into brain networks using independent component analysis (ICA) and&#xD;
      connectivity in these networks patients and controls was compared using dual regression.&#xD;
      FreeSurfer was used to extract brain regions from T1 images and compare the normalised volume&#xD;
      of the hippocampus, amygdala and precuneus for patients and controls. DTI data were analysed&#xD;
      using tract based spatial statistics (TBSS) in FSL and using FreeSurfer regions for the&#xD;
      hippocampus, amygdala and precuneus. Cho/Cr, Cho/NAA and Ins/Cr ratios were extracted from&#xD;
      MRS data using Tarquin. SWI images were reviewed for the presence of microbleeds by two&#xD;
      Radiologists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Neurocognitive deficit</measure>
    <time_frame>Within 10 years of injury</time_frame>
    <description>Median T score of cognitive results (verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>Within 10 years of injury</time_frame>
    <description>EuroQoL 5D score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroinflammation</measure>
    <time_frame>Within 10 years of injury</time_frame>
    <description>As per the functional Magnetic Resonance Imaging protocol</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">30</enrollment>
  <condition>Cognitive Dysfunction</condition>
  <condition>Burns</condition>
  <condition>Inflammation, Brain</condition>
  <condition>Quality of Life</condition>
  <condition>Anxiety</condition>
  <condition>Depression</condition>
  <condition>PostTraumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>Burn patients</arm_group_label>
    <description>Adult survivors of severe burns who have been admitted to Burns ITU for invasive ventilation within 10 years of neurocognitive assessment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Healthy volunteers, controlled for age/sex/IQ</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Severe burns survivors&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Invasive ventilation on a Burns Intensive Care Unit (BICU) within the previous ten&#xD;
             years&#xD;
&#xD;
          -  Burn injuries greater than 15% total body surface area (TBSA)&#xD;
&#xD;
          -  Adult&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Admission to BICU for other illnesses that were not burn related (such as Toxic&#xD;
             Epidermal Necrolysis Syndrome)&#xD;
&#xD;
          -  Evidence of head trauma&#xD;
&#xD;
          -  Known substance misuse or alcohol excess&#xD;
&#xD;
          -  Inability to understand plain verbal or written English&#xD;
&#xD;
          -  Severe mental health issues&#xD;
&#xD;
          -  Receiving formal psychiatric treatment&#xD;
&#xD;
          -  Currently held under the Mental Health Act&#xD;
&#xD;
          -  If the subject's psychological health was deemed to be at risk from inclusion&#xD;
&#xD;
          -  Imprisoned&#xD;
&#xD;
          -  Contraindications to MRI&#xD;
&#xD;
          -  non-compatible pacemakers&#xD;
&#xD;
          -  surgical metalwork or foreign bodies&#xD;
&#xD;
          -  severe claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcela P Vizcaychipi, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anaesthetic and Intensive Care Consultant</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chelsea and Westminster Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>April 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>August 7, 2017</last_update_submitted>
  <last_update_submitted_qc>August 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neuroinflammation</keyword>
  <keyword>fMRI</keyword>
  <keyword>Post-operative cognitive dysfunction</keyword>
  <keyword>Systemic inflammation</keyword>
  <keyword>Severe burns</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Encephalitis</mesh_term>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Burns</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03242395
org study id: 14/LO/0049
nct id: NCT03242395
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Neurocognitive deficit
time frame: Within 10 years of injury
description: Median T score of cognitive results (verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed)
measure: Quality of Life
time frame: Within 10 years of injury
description: EuroQoL 5D score
measure: Neuroinflammation
time frame: Within 10 years of injury
description: As per the functional Magnetic Resonance Imaging protocol
arm group label: Burn patients
description: Adult survivors of severe burns who have been admitted to Burns ITU for invasive ventilation within 10 years of neurocognitive assessment
arm group label: Controls
description: Healthy volunteers, controlled for age/sex/IQ
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Marcela P Vizcaychipi, MD PhD
role: Principal Investigator
affiliation: Anaesthetic and Intensive Care Consultant
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Encephalitis
mesh term: Inflammation
mesh term: Burns
mesh term: Stress Disorders, Post-Traumatic
mesh term: Cognitive Dysfunction
sharing ipd: No