Traumatic Brain InjuryBIO-AX-TBINCT03534154
Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury
An observational study of Traumatic Brain Injury, run by Imperial College London at 5 sites in 4 countries.
Trial summary
Observational longitudinal study assessing outcomes following moderate-severe traumatic brain injury (TBI). Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- MRI, Blood Sampling and Microdialysis
- How many people
- 313 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 30 Nov 2017to 30 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 250 traumatic brain injury patients from ITU / major trauma ward.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Italy2 sites
Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico
Milan
IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"
Milan
About this study
Observational longitudinal study assessing outcomes following moderate-severe traumatic brain injury (TBI).
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- MRI, Blood Sampling, Microdialysis, Neuropsychological tests, MRI (advanced)
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
Magnetic Resonance Imaging
Blood SamplingDiagnostic test
Sampling of serum
MicrodialysisDiagnostic test
Monitoring of cerebral fluid protein levels
Neuropsychological testsDiagnostic test
Battery of tests to assess cognitive function, patient outcomes
MRI (advanced)Diagnostic test
Advanced MRI
| Study group | Role | What they receive |
|---|---|---|
| TBI - MRI / bloods / cognitive / clinical outcomes | Work package 1. In a large multi-centre cohort of adult moderate/severe TBI patients we aim to identify the most informative plasma biomarker(s) of the severity of axonal injury. We will characterise their time course, focusing on neurofilament light (NFL) and tau, and relate these to magnetic resonance imaging (MRI) measures of axonal injury. Using logistic regression we will then test whether these measures contribute to the prediction of clinical outcome at twelve months Receives: Diagnostic Test: MRI; Diagnostic Test: Blood Sampling; Diagnostic Test: Neuropsychological tests | |
| TBI - Advanced MRI / bloods / cognitive / clinical outcomes | Work package 2. In a subgroup of the patients recruited to WP1 we will use advanced MRI and longitudinal assessments to provide a more detailed description of the relationship between the plasma biomarkers and outcome after TBI. We will test whether advanced diffusion and myelin integrity measures correlate with plasma biomarkers and whether early plasma biomarker levels predict neurodegeneration measured by progressive atrophy after TBI. Receives: Diagnostic Test: MRI; Diagnostic Test: Blood Sampling; Diagnostic Test: Neuropsychological tests; Diagnostic Test: MRI (advanced) | |
| TBI - microdialysis / adv. MRI / cognitive / clinical | Work package 3. In a second subgroup of patients recruited to WP1 we will combine microdialysis, neuroimaging and plasma sampling of axonal proteins to provide a deeper understanding of the mechanisms of axonal injury progression and use this approach to investigate the axonal origin of the plasma biomarkers. Receives: Diagnostic Test: MRI; Diagnostic Test: Blood Sampling; Diagnostic Test: Microdialysis; Diagnostic Test: Neuropsychological tests; Diagnostic Test: MRI (advanced) | |
| Healthy volunteer | Single assessment using MRI, bloods and cognitive testing. Receives: Diagnostic Test: MRI; Diagnostic Test: Blood Sampling; Diagnostic Test: Neuropsychological tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in diffusion tensor imaging measures over time
Fractional anisotropy (FA)
Measured: 10 days - 6 weeks, 6 months and 12 months
Brain atrophy rates
Brain tissue volume changes over time.
Measured: 10 days - 6 weeks, 6 months and 12 months
Change in levels of fluid biomarkers in blood
Neurofilament light and Tau protein
Measured: 0-5 days, 5-10 days, 10 days - 6 weeks, 6 months and 12 months
Change in levels of fluid biomarkers in cerebral fluid
Neurofilament light and Tau protein
Measured: 48 hours to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start30 Nov 2017
- Primary completion30 Apr 2021
- Study completion30 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 313 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Vaudois, University College, London, Istituto Di Ricerche Farmacologiche Mario Negri, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Responsible party
- Sponsor
- Investigators
- David Sharp, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03534154
- Sponsor's protocol ID
- 230221
- Other IDs
- MR/R004528/1
- Acronym
- BIO-AX-TBI
- Status last verified
- Mar 2022
- First submitted
- 27 Apr 2018
- Last updated
- 31 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33172948
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT03534154
- Acronym / sponsor ID
- BIO-AX-TBI / 230221
- Conditions
- Traumatic Brain Injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 313 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Vaudois, University College, London, Istituto Di Ricerche Farmacologiche Mario Negri, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Dec 2021 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TBI - MRI / bloods / cognitive / clinical outcomes | – | Diagnostic Test: MRI, Diagnostic Test: Blood Sampling, Diagnostic Test: Neuropsychological testsWork package 1. In a large multi-centre cohort of adult moderate/severe TBI patients we aim to identify the most informative plasma biomarker(s) of the severity of axonal injury. We will characterise their time course, focusing on neurofilament light (NFL) and tau, and relate these to magnetic resonance imaging (MRI) measures of axonal injury. Using logistic regression we will then test whether these measures contribute to the prediction of clinical outcome at twelve months |
| TBI - Advanced MRI / bloods / cognitive / clinical outcomes | – | Diagnostic Test: MRI, Diagnostic Test: Blood Sampling, Diagnostic Test: Neuropsychological tests, Diagnostic Test: MRI (advanced)Work package 2. In a subgroup of the patients recruited to WP1 we will use advanced MRI and longitudinal assessments to provide a more detailed description of the relationship between the plasma biomarkers and outcome after TBI. We will test whether advanced diffusion and myelin integrity measures correlate with plasma biomarkers and whether early plasma biomarker levels predict neurodegeneration measured by progressive atrophy after TBI. |
| TBI - microdialysis / adv. MRI / cognitive / clinical | – | Diagnostic Test: MRI, Diagnostic Test: Blood Sampling, Diagnostic Test: Microdialysis, Diagnostic Test: Neuropsychological tests, Diagnostic Test: MRI (advanced)Work package 3. In a second subgroup of patients recruited to WP1 we will combine microdialysis, neuroimaging and plasma sampling of axonal proteins to provide a deeper understanding of the mechanisms of axonal injury progression and use this approach to investigate the axonal origin of the plasma biomarkers. |
| Healthy volunteer | – | Diagnostic Test: MRI, Diagnostic Test: Blood Sampling, Diagnostic Test: Neuropsychological testsSingle assessment using MRI, bloods and cognitive testing. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 250 traumatic brain injury patients from ITU / major trauma ward.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIMagnetic Resonance Imaging | Diagnostic test | Healthy volunteer, TBI - Advanced MRI / bloods / cognitive / clinical outcomes, TBI - MRI / bloods / cognitive / clinical outcomes, TBI - microdialysis / adv. MRI / cognitive / clinical |
| Blood SamplingSampling of serum | Diagnostic test | Healthy volunteer, TBI - Advanced MRI / bloods / cognitive / clinical outcomes, TBI - MRI / bloods / cognitive / clinical outcomes, TBI - microdialysis / adv. MRI / cognitive / clinical |
| MicrodialysisMonitoring of cerebral fluid protein levels | Diagnostic test | TBI - microdialysis / adv. MRI / cognitive / clinical |
| Neuropsychological testsBattery of tests to assess cognitive function, patient outcomes | Diagnostic test | Healthy volunteer, TBI - Advanced MRI / bloods / cognitive / clinical outcomes, TBI - MRI / bloods / cognitive / clinical outcomes, TBI - microdialysis / adv. MRI / cognitive / clinical |
| MRI (advanced)Advanced MRI | Diagnostic test | TBI - Advanced MRI / bloods / cognitive / clinical outcomes, TBI - microdialysis / adv. MRI / cognitive / clinical |
Primary outcome
Change in diffusion tensor imaging measures over time
Time frame: 10 days - 6 weeks, 6 months and 12 months
Fractional anisotropy (FA)
Brain atrophy rates
Time frame: 10 days - 6 weeks, 6 months and 12 months
Brain tissue volume changes over time.
Change in levels of fluid biomarkers in blood
Time frame: 0-5 days, 5-10 days, 10 days - 6 weeks, 6 months and 12 months
Neurofilament light and Tau protein
Change in levels of fluid biomarkers in cerebral fluid
Time frame: 48 hours to 7 days
Neurofilament light and Tau protein
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Background: PubMed 33172948Graham 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Sharp principal investigator
Imperial College London
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury, run by Imperial College London at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy, Slovenia, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in diffusion tensor imaging measures over time (time frame: 10 days - 6 weeks, 6 months and 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03534154, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.