Long-term Follow-up in Severe Traumatic Brain Injury

Recruiting

• Conditions: Neurodegenerative Diseases; Traumatic Brain Injury; Chronic Traumatic Encephalopathy
• Interventions: Diagnostic Test: Magnetic Resonance Imaging (MRI) (including functional MRI); Diagnostic Test: Blood sampling (serum/plasma preparation); Diagnostic Test: Cerebrospinal fluid (CSF); Diagnostic Test: Clinical assessments / questionnaires

• Registration Number: NCT05235802
• Lead Sponsor: Karolinska University Hospital

Brief Summary

The underlying pathophysiology following traumatic brain injury (TBI) in how different neurodegenerative conditions are developed are still unknown. Different neuroinflammatory and neurodegenerative pathways have been suggested.

The goal of this study is to follow-up patients that have been treated for TBI at the neurosurgical department about 10-15 years after their initial injury, in order to analyze fluid biomarkers of inflammation, injury and degeneration and associate these with structural imaging and long-term functional outcome.

The investigators aim to invite about 100 patients back and perform advanced magnetic resonance imaging protocols, sample cerebrospinal fluid and blood for different bio- and inflammatory markers, study genetic modifications and associate it with outcomes being assessed through questionnaires.

The investigators' hypothesis is that patients with ongoing inflammatory processes will present with more fluid biomarkers of neurodegeneration, worse clinical presentation and also more structural/atrophic signs on imaging. This will result in an increased understanding of the interplay between neuroinflammation and neurodegeneration in chronic TBI, as well as a panel of tentative biomarkers that could be used to assess level of disability following TBI and chronic traumatic encephalopathy (CTE).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-24
• Study Start: 2021-10-01
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-01
• Last Update Submitted: 2022-02-01
• Study First Posted: 2022-02-11
• Last Update Posted: 2022-02-11
• Primary Completion: 2023-01-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Having suffered a traumatic brain injury and being treated at the Karolinska University Hospital between 2007 and 2015.
• Age >18 years of age

Exclusion Criteria

• Pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with traumatic brain injury about 10 years ago	Magnetic Resonance Imaging (MRI) (including functional MRI)	Patients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015.
Patients with traumatic brain injury about 10 years ago	Cerebrospinal fluid (CSF)	Patients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015.
Patients with traumatic brain injury about 10 years ago	Blood sampling (serum/plasma preparation)	Patients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015.
Patients with traumatic brain injury about 10 years ago	Clinical assessments / questionnaires	Patients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015.

Primary Outcome Measures

Name	Time	Method
MADRS vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Montgomery-Åsberg depression rating scale (MADRS) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (MADRS score vs affected voxels).
Structural outcome vs auto-antibodies in serum	Assessed at the chronic time-point (10-15 years after injury).	Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a panel of auto-antibodies targeting central nervous system antigens ((affected voxels vs antibody titers)
Fatigue Severity Scale vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Fatigue Severity Scale (9-63) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
MOCA vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Montreal Cognitive Assessment (MoCA) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (MOCA score vs affected voxels).
EQ-5D vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Health-related quality of life (EQ-5D) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (EQ5D score vs affected voxels on MRI).
Barthel Index vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Barthel Index (0-100) will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
SF-36 vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Short-Form 36 will be associated with alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (SF-36 score vs affected voxels on MRI).
GOSE vs structural outcome	Assessed at the chronic time-point (10-15 years after injury).	Glasgow Outcome Score extended (1-8) will be associated alterations at axonal and myelin integrity as assessed by magnetic resonance imaging (affected voxels).
Structural outcome vs proteomic markers in serum	Assessed at the chronic time-point (10-15 years after injury).	Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin (affected voxels vs mean fluorescent intensities (MFI)).
Structural outcome vs proteomic markers in cerebrospinal fluid	Assessed at the chronic time-point (10-15 years after injury).	Alterations at axonal and myelin integrity as assessed by magnetic resonance imaging will be associated with a proteomic profiling of cerebrospinal fluid using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin (affected voxels vs mean fluorescent intensities (MFI)).

Secondary Outcome Measures

Name	Time	Method
Acute vs chronic comparisons of proteomic markers in CSF	From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)	Proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin in CSF will be compared in a subset of patients between the acute and chronic stage comparing mean flourescent intensities (MFI).
Acute vs chronic comparisons of autoantibodies	From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)	A panel of auto-antibodies targeting central nervous system antigens will be compared between the acute and chronic phase (comparison of antibody titers)
Acute vs chronic comparisons of proteomic markers in serum	From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)	Proteomic profiling using a targeted antibody array of about 30 proteins of inflammatory and neurodegenerative origin will be compared in a subset of patients between the acute and chronic stage comparing mean flourescent intensities (MFI).

Trial Locations

Locations (1)

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden