Cognitive and Blood Biomarker Assessment After CO Exposure

Cognitive, Behavioural and Blood Biomarker Assessment After Carbon Monoxide (CO) Exposure

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.

Study Overview

• Status: Unknown
• Conditions: Carbon Monoxide Poisoning

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Peter O Jenkins, PhD; Phone Number: 020 82666866; Email: peter.jenkins1@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

50 individuals with confirmed evidence of CO exposure will be recruited.

Description

Inclusion Criteria:

Individuals identified as having confirmed exposure to CO between 2 weeks to 2 years at time of assessment. CO exposure determined by either;

• documented COHb levels above 1.6% in non-smokers and above 6.3% in smokers.
• or, individuals with evidence of being exposed to raised levels of CO and symptoms

Exclusion Criteria:

• age <18 years
• actual or suspected smoke inhalation
• significant neurological or psychiatric illness prior to CO exposure
• inability to provide consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Carbon monoxide exposure; Confirmed exposure to carbon monoxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood biomarker level of neurofilament light in participants with proven CO exposure.	Plasma levels of neurofilament light will be measured	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood biomarker level of tau in participants with proven CO exposure.	Plasma levels of tau will be measured	18 months
Blood biomarker level of glial fibrillary acidic protein in participants with proven CO exposure.	Plasma levels of glial fibrillary acidic protein will be measured	18 months
Behavioural questionnaire: depression (Patient Health Questionnaire - part 9)	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.	18 months
Behavioural questionnaire: anxiety (Generalised Anxiety Disorder Questionnaire - GAD7)	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.	18 months
Behavioural questionnaire: post-traumatic stress symptoms (Impact of Events Scale)	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.	18 months
Behavioural questionnaire: Attentional behaviour (Rating Scale of Attentional Behaviour)	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.	18 months
Behavioural questionnaire: fatigue (Visual Analogue Scale of Fatigue)	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.	18 months
Behavioural questionnaire: Quality of life (The Short Form (36) Health Survey)	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.	18 months
Behavioural questionnaire: return to work/social activities (Work and Social Adjustment Scale)	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.	18 months
Cognitive assessment	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.	18 months

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: University College, London
• Investigators: Principal Investigator: Peter O Jenkins, PhD, St. George's Hospital, London

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Gas Poisoning; Poisoning; Carbon Monoxide Poisoning
• Other Study ID Numbers: 2019.0375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan 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 Sharing 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 Sharing Access Criteria: Researchers who provide a methodologically sound proposal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No