Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— BIO-AX-TBI  

Official title:

Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03534154
• Other study ID #: 230221
• Secondary ID: MR/R004528/1
• Status: Completed
• Start date: November 30, 2017
• Est. completion date: December 30, 2021

Study information

• Verified date: March 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: December 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Diagnostic Test:
• MRI
Magnetic Resonance Imaging
• Blood Sampling
Sampling of serum
• Microdialysis
Monitoring of cerebral fluid protein levels
• Neuropsychological tests
Battery of tests to assess cognitive function, patient outcomes
• MRI (advanced)
Advanced MRI

Locations

Country	Name	City	State
Italy	Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico	Milan
Italy	IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"	Milan
Slovenia	University Medical Centre	Ljubljana
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Imperial College London	London

Sponsors (5)

Lead Sponsor	Collaborator
Imperial College London	Centre Hospitalier Universitaire Vaudois, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Istituto Di Ricerche Farmacologiche Mario Negri, University College, London

Countries where clinical trial is conducted

Italy,  Slovenia,  Switzerland,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in diffusion tensor imaging measures over time	Fractional anisotropy (FA)	10 days - 6 weeks, 6 months and 12 months
Primary	Brain atrophy rates	Brain tissue volume changes over time.	10 days - 6 weeks, 6 months and 12 months
Primary	Change in levels of fluid biomarkers in blood	Neurofilament light and Tau protein	0-5 days, 5-10 days, 10 days - 6 weeks, 6 months and 12 months
Primary	Change in levels of fluid biomarkers in cerebral fluid	Neurofilament light and Tau protein	48 hours to 7 days