<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/NCT04475263</url>
  </required_header>
  <id_info>
    <org_study_id>2019.0375</org_study_id>
    <nct_id>NCT04475263</nct_id>
  </id_info>
  <brief_title>Cognitive and Blood Biomarker Assessment After CO Exposure</brief_title>
  <official_title>Cognitive, Behavioural and Blood Biomarker Assessment After Carbon Monoxide (CO) Exposure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St George's, University of London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St George's, 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>
      Carbon monoxide (CO) is reported to cause around 30 deaths, 200 admissions and 4000&#xD;
      presentations to Emergency Departments each year in the UK. In the longer term, CO poisoning&#xD;
      is recognised to cause persistent neurological problems (including impairments of thinking&#xD;
      and behavioural changes), which can develop days to weeks after the initial exposure.&#xD;
      However, the incidence of these long-term sequelae is unknown. In addition, there is evidence&#xD;
      of long-lasting inflammatory changes in the brain and on-going brain cell injury, although&#xD;
      how long this persists is also unknown.&#xD;
&#xD;
      Initial assessments of CO exposure can be unreliable if blood tests are not carried out&#xD;
      within a relatively short period after the exposure and other biomarkers (such as imaging)&#xD;
      are insensitive to detecting previous CO exposure. Certain proteins that are found in brain&#xD;
      cells can be detected in the blood of individuals following brain injury and brain cell&#xD;
      death. These proteins have been found to be raised in the acute period after minor head&#xD;
      injury, persistently raised in patients with a traumatic brain injury and evidence of on&#xD;
      going neurodegeneration (i.e. on going brain cell death) and in patients with various types&#xD;
      of dementia.&#xD;
&#xD;
      The investigators will assess the presence of these proteins in the blood of 50 participants&#xD;
      with proven CO exposure in the sub-acute to chronic timescale (2 weeks to 2 years). This has&#xD;
      not been done before and will allow assessment of the presence of on going brain injury in&#xD;
      these participants. The investigators will also assess cognitive (e.g. memory, attention and&#xD;
      speed of thinking) and behavioural impairments in these participants to help characterise the&#xD;
      common impairments suffered following CO exposure and relate these to evidence of persistent&#xD;
      brain injury and severity of CO exposure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Blood biomarker level of neurofilament light in participants with proven CO exposure.</measure>
    <time_frame>18 months</time_frame>
    <description>Plasma levels of neurofilament light will be measured</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood biomarker level of tau in participants with proven CO exposure.</measure>
    <time_frame>18 months</time_frame>
    <description>Plasma levels of tau will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood biomarker level of glial fibrillary acidic protein in participants with proven CO exposure.</measure>
    <time_frame>18 months</time_frame>
    <description>Plasma levels of glial fibrillary acidic protein will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: depression (Patient Health Questionnaire - part 9)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete a validated questionnaire assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: anxiety (Generalised Anxiety Disorder Questionnaire - GAD7)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: post-traumatic stress symptoms (Impact of Events Scale)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: Attentional behaviour (Rating Scale of Attentional Behaviour)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: fatigue (Visual Analogue Scale of Fatigue)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: Quality of life (The Short Form (36) Health Survey)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioural questionnaire: return to work/social activities (Work and Social Adjustment Scale)</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive assessment</measure>
    <time_frame>18 months</time_frame>
    <description>Participants will complete a battery of cognitive assessments with a large normative control population. Cognitive tests will assess speed of information processing, reasoning, memory and visuospatial abilities. All results will be a numerical result.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Carbon Monoxide Poisoning</condition>
  <arm_group>
    <arm_group_label>Carbon monoxide exposure</arm_group_label>
    <description>Confirmed exposure to carbon monoxide</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        50 individuals with confirmed evidence of CO exposure will be recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Individuals identified as having confirmed exposure to CO between 2 weeks to 2 years at&#xD;
        time of assessment. CO exposure determined by either;&#xD;
&#xD;
          -  documented COHb levels above 1.6% in non-smokers and above 6.3% in smokers.&#xD;
&#xD;
          -  or, individuals with evidence of being exposed to raised levels of CO and symptoms&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt;18 years&#xD;
&#xD;
          -  actual or suspected smoke inhalation&#xD;
&#xD;
          -  significant neurological or psychiatric illness prior to CO exposure&#xD;
&#xD;
          -  inability to provide consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter O Jenkins, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. George's Hospital, London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peter O Jenkins, PhD</last_name>
    <phone>020 82666866</phone>
    <email>peter.jenkins1@nhs.net</email>
  </overall_contact>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>March 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</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>Poisoning</mesh_term>
    <mesh_term>Carbon Monoxide Poisoning</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in this article, after deidentification. Proposals should be directed to peter.jenkins1@nhs.net. To gain access, data requestors will need to sign a data access agreement.</ipd_description>
    <ipd_time_frame>Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.</ipd_time_frame>
    <ipd_access_criteria>Researchers who provide a methodologically sound proposal.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 14, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT04475263/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04475263
org study id: 2019.0375
nct id: NCT04475263
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Carbon monoxide (CO) is reported to cause around 30 deaths, 200 admissions and 4000
      presentations to Emergency Departments each year in the UK. In the longer term, CO poisoning
      is recognised to cause persistent neurological problems (including impairments of thinking
      and behavioural changes), which can develop days to weeks after the initial exposure.
      However, the incidence of these long-term sequelae is unknown. In addition, there is evidence
      of long-lasting inflammatory changes in the brain and on-going brain cell injury, although
      how long this persists is also unknown.

      Initial assessments of CO exposure can be unreliable if blood tests are not carried out
      within a relatively short period after the exposure and other biomarkers (such as imaging)
      are insensitive to detecting previous CO exposure. Certain proteins that are found in brain
      cells can be detected in the blood of individuals following brain injury and brain cell
      death. These proteins have been found to be raised in the acute period after minor head
      injury, persistently raised in patients with a traumatic brain injury and evidence of on
      going neurodegeneration (i.e. on going brain cell death) and in patients with various types
      of dementia.

      The investigators will assess the presence of these proteins in the blood of 50 participants
      with proven CO exposure in the sub-acute to chronic timescale (2 weeks to 2 years). This has
      not been done before and will allow assessment of the presence of on going brain injury in
      these participants. The investigators will also assess cognitive (e.g. memory, attention and
      speed of thinking) and behavioural impairments in these participants to help characterise the
      common impairments suffered following CO exposure and relate these to evidence of persistent
      brain injury and severity of CO exposure.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Blood biomarker level of neurofilament light in participants with proven CO exposure.
time frame: 18 months
description: Plasma levels of neurofilament light will be measured
measure: Blood biomarker level of tau in participants with proven CO exposure.
time frame: 18 months
description: Plasma levels of tau will be measured
measure: Blood biomarker level of glial fibrillary acidic protein in participants with proven CO exposure.
time frame: 18 months
description: Plasma levels of glial fibrillary acidic protein will be measured
measure: Behavioural questionnaire: depression (Patient Health Questionnaire - part 9)
time frame: 18 months
description: Participants will be asked to complete a validated questionnaire assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: anxiety (Generalised Anxiety Disorder Questionnaire - GAD7)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: post-traumatic stress symptoms (Impact of Events Scale)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: Attentional behaviour (Rating Scale of Attentional Behaviour)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: fatigue (Visual Analogue Scale of Fatigue)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: Quality of life (The Short Form (36) Health Survey)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Behavioural questionnaire: return to work/social activities (Work and Social Adjustment Scale)
time frame: 18 months
description: Participants will be asked to complete validated questionnaires assessing fatigue, depression, anxiety, post-traumatic stress symptoms, problems with attention, quality of life, return to work and illness perceptions. All questionnaires provide a numerical score.
measure: Cognitive assessment
time frame: 18 months
description: Participants will complete a battery of cognitive assessments with a large normative control population. Cognitive tests will assess speed of information processing, reasoning, memory and visuospatial abilities. All results will be a numerical result.
arm group label: Carbon monoxide exposure
description: Confirmed exposure to carbon monoxide
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter O Jenkins, PhD
role: Principal Investigator
affiliation: St. George's Hospital, London
last name: Peter O Jenkins, PhD
phone: 020 82666866
email: peter.jenkins1@nhs.net
responsible party type: Sponsor
mesh term: Poisoning
mesh term: Carbon Monoxide Poisoning
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in this article, after deidentification. Proposals should be directed to peter.jenkins1@nhs.net. To gain access, data requestors will need to sign a data access agreement.
ipd time frame: Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
ipd access criteria: Researchers who provide a methodologically sound proposal.
provided document: 