Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury (BIO-AX-TBI)

March 29, 2022 updated by: Imperial College London
Observational longitudinal study assessing outcomes following moderate-severe traumatic brain injury (TBI).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
313

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy
        • Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico
      • Milan, Italy
        • IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"
  • Slovenia
      • Ljubljana, Slovenia
        • University Medical Centre
  • Switzerland
      • Lausanne, Switzerland
        • Centre Hospitalier Universitaire Vaudois
  • United Kingdom
      • London, United Kingdom, W12 0NN
        • Imperial College London

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

250 traumatic brain injury patients from ITU / major trauma ward.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Diagnostic test: MRI
Magnetic Resonance Imaging
Diagnostic test: Blood Sampling
Sampling of serum
Diagnostic test: Neuropsychological tests
Battery of tests to assess cognitive function, patient outcomes
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.
Diagnostic test: MRI
Magnetic Resonance Imaging
Diagnostic test: Blood Sampling
Sampling of serum
Diagnostic test: Neuropsychological tests
Battery of tests to assess cognitive function, patient outcomes
Diagnostic test: MRI (advanced)
Advanced MRI
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.
Diagnostic test: MRI
Magnetic Resonance Imaging
Diagnostic test: Blood Sampling
Sampling of serum
Diagnostic test: Neuropsychological tests
Battery of tests to assess cognitive function, patient outcomes
Diagnostic test: MRI (advanced)
Advanced MRI
Diagnostic test: Microdialysis
Monitoring of cerebral fluid protein levels
Healthy volunteer
Single assessment using MRI, bloods and cognitive testing.
Diagnostic test: MRI
Magnetic Resonance Imaging
Diagnostic test: Blood Sampling
Sampling of serum
Diagnostic test: Neuropsychological tests
Battery of tests to assess cognitive function, patient outcomes

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in diffusion tensor imaging measures over time
Time Frame: 10 days - 6 weeks, 6 months and 12 months
Fractional anisotropy (FA)
10 days - 6 weeks, 6 months and 12 months
Brain atrophy rates
Time Frame: 10 days - 6 weeks, 6 months and 12 months
Brain tissue volume changes over time.
10 days - 6 weeks, 6 months and 12 months
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
0-5 days, 5-10 days, 10 days - 6 weeks, 6 months and 12 months
Change in levels of fluid biomarkers in cerebral fluid
Time Frame: 48 hours to 7 days
Neurofilament light and Tau protein
48 hours to 7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Imperial College London

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University College, London
Centre Hospitalier Universitaire Vaudois
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Istituto Di Ricerche Farmacologiche Mario Negri

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David Sharp, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 230221
  • MR/R004528/1 (Other Grant/Funding Number: ERA-NET)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings