NCT03534154

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
313

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Nov 2017

Longer than P75 for all trials

Geographic Reach
4 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 30, 2017

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

April 27, 2018

Completed
26 days until next milestone

First Posted

Study publicly available on registry

May 23, 2018

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2021

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2021

Completed
Last Updated

March 31, 2022

Status Verified

March 1, 2022

Enrollment Period

3.4 years

First QC Date

April 27, 2018

Last Update Submit

March 29, 2022

Conditions

Outcome Measures

Primary Outcomes (4)

  • Change in diffusion tensor imaging measures over time

    Fractional anisotropy (FA)

    10 days - 6 weeks, 6 months and 12 months

  • Brain atrophy rates

    Brain tissue volume changes over time.

    10 days - 6 weeks, 6 months and 12 months

  • 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

  • Change in levels of fluid biomarkers in cerebral fluid

    Neurofilament light and Tau protein

    48 hours to 7 days

Study Arms (4)

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: MRIDiagnostic Test: Blood SamplingDiagnostic 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.

Diagnostic Test: MRIDiagnostic Test: Blood SamplingDiagnostic Test: Neuropsychological testsDiagnostic 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.

Diagnostic Test: MRIDiagnostic Test: Blood SamplingDiagnostic Test: MicrodialysisDiagnostic Test: Neuropsychological testsDiagnostic Test: MRI (advanced)

Healthy volunteer

Single assessment using MRI, bloods and cognitive testing.

Diagnostic Test: MRIDiagnostic Test: Blood SamplingDiagnostic Test: Neuropsychological tests

Interventions

MRIDIAGNOSTIC_TEST

Magnetic Resonance Imaging

Healthy volunteerTBI - Advanced MRI / bloods / cognitive / clinical outcomesTBI - MRI / bloods / cognitive / clinical outcomesTBI - microdialysis / adv. MRI / cognitive / clinical
Blood SamplingDIAGNOSTIC_TEST

Sampling of serum

Healthy volunteerTBI - Advanced MRI / bloods / cognitive / clinical outcomesTBI - MRI / bloods / cognitive / clinical outcomesTBI - microdialysis / adv. MRI / cognitive / clinical
MicrodialysisDIAGNOSTIC_TEST

Monitoring of cerebral fluid protein levels

TBI - microdialysis / adv. MRI / cognitive / clinical

Battery of tests to assess cognitive function, patient outcomes

Healthy volunteerTBI - Advanced MRI / bloods / cognitive / clinical outcomesTBI - MRI / bloods / cognitive / clinical outcomesTBI - microdialysis / adv. MRI / cognitive / clinical
MRI (advanced)DIAGNOSTIC_TEST

Advanced MRI

TBI - Advanced MRI / bloods / cognitive / clinical outcomesTBI - microdialysis / adv. MRI / cognitive / clinical

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"

Milan, Italy

Location

University Medical Centre

Ljubljana, Slovenia

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Imperial College London

London, W12 0NN, United Kingdom

Location

Related 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.

    PMID: 33172948BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and cerebral microdialysis samples collected during longitudinal study, where appropriate (as per protocol).

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Blood Specimen CollectionMagnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative TechniquesTomographyDiagnostic Imaging

Study Officials

  • David Sharp

    Imperial College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2018

First Posted

May 23, 2018

Study Start

November 30, 2017

Primary Completion

April 30, 2021

Study Completion

December 30, 2021

Last Updated

March 31, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations