<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/NCT04418440</url>
  </required_header>
  <id_info>
    <org_study_id>273132</org_study_id>
    <nct_id>NCT04418440</nct_id>
  </id_info>
  <brief_title>Nutritional Treatment for the Amelioration of Traumatic Brain Injury</brief_title>
  <acronym>NUTRA-TBI</acronym>
  <official_title>Nutritional Treatment for the Amelioration of Traumatic Brain Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen Mary University of London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen Mary University of London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To test the feasibility of administering a commercially available neurotrophic oral&#xD;
      nutritional supplement (ONS) for adult patients with acute traumatic brain injury at the&#xD;
      Royal London Hospital.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a randomised controlled non-blinded trial of adult patients with acute&#xD;
      traumatic brain injury at the Royal London Hospital.&#xD;
&#xD;
      There will be randomisation to one of two non-blinded trial groups:&#xD;
&#xD;
        1. Usual standard NHS care (control group)&#xD;
&#xD;
        2. Usual standard NHS care plus daily oral dose of Souvenaid® ONS&#xD;
&#xD;
      The trial protocol will commence between 3-7 days after admission. The trial timeline&#xD;
      provides a summary of intervention and assessments.&#xD;
&#xD;
      The trial will last 12 months. The first 6 months will be the formal trial with two groups&#xD;
      and follow up assessments. This will be performed on intention to treat basis. After this&#xD;
      initial phase the investigators will provide an opportunity for all participants from either&#xD;
      group (control or treatment) to take Souvenaid® ONS for a further 6 months with a clinical&#xD;
      follow up appointment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 14, 2021</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility to conduct the protocol as stated</measure>
    <time_frame>10 months</time_frame>
    <description>To assess logistical issues which might prevent a fully powered study being carried out using this protocol. The investigators will primarily be looking at retention rate. If there is an attrition rate of over 80% then this protocol will be deemed not feasible.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brain network connectivity</measure>
    <time_frame>10 months</time_frame>
    <description>As measured by resting state EEG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>10 months</time_frame>
    <description>Changes to cognitive function as measure by CANTAB-TBI cognitive test. This is a validated and widely used clinical tool for cognitive assessment in TBI and assesses cognition using the following battery of tests (range of scores in brackets with lower score being worse performance and higher being better performance): paired associates learning (0-70); reaction time (100-5100); spatial working memory (0-153); multitasking test (0-160); one touch stockings of Cambridge (0-15).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma phospholipid levels</measure>
    <time_frame>10 months</time_frame>
    <description>Plasma phospholipid levels will be measured using thin layer chromatography and/or LC-MS. Batch analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Omega-3 index</measure>
    <time_frame>10 months</time_frame>
    <description>The omega-3 index will be analysed in red blood cells. Therefore, lipids will be extracted from red blood cells, followed by transesterification and quantification using gas chromatography coupled to a flame ionisation detector.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurofilament light levels</measure>
    <time_frame>10 months</time_frame>
    <description>Plasma or serum neurofilament light levels will be measured using either a commercially available enzyme-linked immunosorbent assay, a commercially available chemi-luminescent assay, or the commercially available SIMOA assay. Combined samples will be run on each plate to account for inter plate variability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory markers</measure>
    <time_frame>10 months</time_frame>
    <description>Inflammatory markers such as cytokines will be analysed using either enzyme-linked immunosorbent assays or a multiplex system. Combined samples will be run on each plate to account for inter plate variability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein</measure>
    <time_frame>10 months</time_frame>
    <description>CRP will be measured independently using an enzyme-linked immunosorbent assay. Combined samples will be run on each plate to account for inter plate variability</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Routine NHS care following traumatic brain injury</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Routine NHS care following traumatic brain injury plus daily dose of test compound (oral nutritional supplement)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Souvenaid oral nutritional supplement (Nutricia)</intervention_name>
    <description>Daily dose of a commercially available oral nutritional supplement based around the active compound recipe Fortasyn Connect, produced by Nutricia, Danone.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult between 18 yrs and 80 yrs of age&#xD;
&#xD;
          -  Acute traumatic brain injury with confirmed radiological features&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergies to fish oil/milk/soya&#xD;
&#xD;
          -  Medical history of galactosaemia&#xD;
&#xD;
          -  Non-traumatic aetiology to head injury&#xD;
&#xD;
          -  Unable to receive enteral nutrition&#xD;
&#xD;
          -  Craniectomy during admission (loss of integrity of skull convexity)&#xD;
&#xD;
          -  Concurrent active neurological disease&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris Uff</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barts Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bart Health, Royal London Hospital</name>
      <address>
        <city>London</city>
        <zip>E1 1FR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>August 14, 2023</last_update_submitted>
  <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Not applicable, not part of protocol</ipd_description>
  </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/NCT04418440
org study id: 273132
nct id: NCT04418440
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To test the feasibility of administering a commercially available neurotrophic oral
      nutritional supplement (ONS) for adult patients with acute traumatic brain injury at the
      Royal London Hospital.
The study will be a randomised controlled non-blinded trial of adult patients with acute
      traumatic brain injury at the Royal London Hospital.

      There will be randomisation to one of two non-blinded trial groups:

        1. Usual standard NHS care (control group)

        2. Usual standard NHS care plus daily oral dose of Souvenaid® ONS

      The trial protocol will commence between 3-7 days after admission. The trial timeline
      provides a summary of intervention and assessments.

      The trial will last 12 months. The first 6 months will be the formal trial with two groups
      and follow up assessments. This will be performed on intention to treat basis. After this
      initial phase the investigators will provide an opportunity for all participants from either
      group (control or treatment) to take Souvenaid® ONS for a further 6 months with a clinical
      follow up appointment.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility to conduct the protocol as stated
time frame: 10 months
description: To assess logistical issues which might prevent a fully powered study being carried out using this protocol. The investigators will primarily be looking at retention rate. If there is an attrition rate of over 80% then this protocol will be deemed not feasible.
measure: Brain network connectivity
time frame: 10 months
description: As measured by resting state EEG
measure: Cognitive function
time frame: 10 months
description: Changes to cognitive function as measure by CANTAB-TBI cognitive test. This is a validated and widely used clinical tool for cognitive assessment in TBI and assesses cognition using the following battery of tests (range of scores in brackets with lower score being worse performance and higher being better performance): paired associates learning (0-70); reaction time (100-5100); spatial working memory (0-153); multitasking test (0-160); one touch stockings of Cambridge (0-15).
measure: Plasma phospholipid levels
time frame: 10 months
description: Plasma phospholipid levels will be measured using thin layer chromatography and/or LC-MS. Batch analysis
measure: Omega-3 index
time frame: 10 months
description: The omega-3 index will be analysed in red blood cells. Therefore, lipids will be extracted from red blood cells, followed by transesterification and quantification using gas chromatography coupled to a flame ionisation detector.
measure: Neurofilament light levels
time frame: 10 months
description: Plasma or serum neurofilament light levels will be measured using either a commercially available enzyme-linked immunosorbent assay, a commercially available chemi-luminescent assay, or the commercially available SIMOA assay. Combined samples will be run on each plate to account for inter plate variability.
measure: Inflammatory markers
time frame: 10 months
description: Inflammatory markers such as cytokines will be analysed using either enzyme-linked immunosorbent assays or a multiplex system. Combined samples will be run on each plate to account for inter plate variability.
measure: C-reactive protein
time frame: 10 months
description: CRP will be measured independently using an enzyme-linked immunosorbent assay. Combined samples will be run on each plate to account for inter plate variability
arm group label: Control
arm group type: No Intervention
description: Routine NHS care following traumatic brain injury
arm group label: Treatment
arm group type: Experimental
description: Routine NHS care following traumatic brain injury plus daily dose of test compound (oral nutritional supplement)
intervention type: Dietary Supplement
intervention name: Souvenaid oral nutritional supplement (Nutricia)
description: Daily dose of a commercially available oral nutritional supplement based around the active compound recipe Fortasyn Connect, produced by Nutricia, Danone.
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Chris Uff
role: Principal Investigator
affiliation: Barts Health
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries
sharing ipd: No
ipd description: Not applicable, not part of protocol