Clinical trial NCT03534154: Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury
Official title: Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire Vaudois
name: University College, London
name: Istituto Di Ricerche Farmacologiche Mario Negri
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
First posted: 2018-05-23
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 250 traumatic brain injury patients from ITU / major trauma ward.

Brief summary: Observational longitudinal study assessing outcomes following moderate-severe traumatic brain injury (TBI).

Detailed description: Traumatic brain injury (TBI) occurs when the brain is physically damaged, for example after a car crash. It is common and survivors often have major on-going problems. It is very difficult to predict how patients will do after TBI. One reason for this is that clinicians and researchers are unable to measure all the effects of TBI. An important factor is that the connections between nerve cells are damaged by the impact on the brain of an injury (axonal injury). This damage has been difficult to measure in the past, but new ways to scan the brain and more sensitive ways of picking up the effects of this injury in the blood could change this. In other parts of medicine tests of this type have had a dramatic effect on how clinicians treat patients. For example, the products of heart muscle damage that have leaked into the blood can be used identify a heart attack and guide treatment. Clinicians need similar tests to be available in TBI. This should be possible as the products of axonal injury also leak into the blood and researchers have a sensitive way to pick this up. An accurate test for axonal injury would guide treatment choices and allow clinicians to predict how patients will recover. The investigators have brought together an international team who have been working on different aspects of this problem for many years. Together the investigators will conduct a large study to identify the best measures of axonal injury. The investigators will carefully test whether these measures help predict outcomes and will study where the blood markers come from using a safe method to measure the effects of axonal injury directly from the brain. The work links into some large projects that have already started and will use a standard way to assess patients after their injury. This is important because it will allow researchers to share results across studies. The investigators hope the work will allow us to identify a blood marker for TBI that could be widely used to quickly identify the presence of axonal injury. The investigators will also show what brain imaging measure is best at picking up axonal injury and how best to combine the measures to best predict how patients recover. This will allow doctors to diagnose problems after TBI more accurately, choose the right treatments and give patients and their families accurate advice about what will happen after discharge from hospital.

Eligibility criteria: Inclusion Criteria:

* A diagnosis of moderate/severe traumatic brain injury (TBI) as classified using the Mayo classification system;
* Healthy controls will be age-matched to our TBI patients and will not have a history of significant neurological or psychiatric conditions.

Exclusion Criteria:

* Unwillingness or inability to follow the procedures required
* Bilateral fixed dilated pupils
* For MRI, contra-indication to MRI scanning, assessed by a standard pre-MRI questionnaire (e.g. presence of ferromagnetic implants in the body, claustrophobia, pregnancy) if considered for the imaging strand of the study.

Primary outcomes:
measure: Change in diffusion tensor imaging measures over time
timeFrame: 10 days - 6 weeks, 6 months and 12 months
measure: Brain atrophy rates
timeFrame: 10 days - 6 weeks, 6 months and 12 months
measure: Change in levels of fluid biomarkers in blood
timeFrame: 0-5 days, 5-10 days, 10 days - 6 weeks, 6 months and 12 months
measure: Change in levels of fluid biomarkers in cerebral fluid
timeFrame: 48 hours to 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"
city: Ljubljana
country: Slovenia
facility: University Medical Centre
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Imperial College London
name: David Sharp
role: PRINCIPAL_INVESTIGATOR
References:
citation: Graham NSN, Zimmerman KA, Bertolini G, Magnoni S, Oddo M, Zetterberg H, Moro F, Novelli D, Heslegrave A, Chieregato A, Fainardi E, Fleming JM, Garbero E, Abed-Maillard S, Gradisek P, Bernini A, Sharp DJ. Multicentre longitudinal study of fluid and neuroimaging BIOmarkers of AXonal injury after traumatic brain injury: the BIO-AX-TBI study protocol. BMJ Open. 2020 Nov 10;10(11):e042093. doi: 10.1136/bmjopen-2020-042093.