Long-term Follow-up in Severe Traumatic Brain Injury (LONG-TBI)

February 1, 2022 updated by: Eric Thelin, Karolinska University Hospital

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients that had suffered a traumatic brain injury and registered at our local trauma database will be sent a letter asking them for participation.

Description

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 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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with traumatic brain injury about 10 years ago
Patients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015.
Diagnostic test: Magnetic Resonance Imaging (MRI) (including functional MRI)

Patients will undergo magnetic resonance imaging including the following protocols:

  • 3D T1w MPRAGE
  • 3D T2w FLAIR SPACE
  • 3D T2w SPACE
  • 3D T1w PSIR (cortical visualization)
  • 2D synthetic MRI (quantitative T1, T2, PD and myelin quantification)
  • Resting-state fMRI (6 min, human connectome protocol, 2 mm iso)
  • 3D SWI
  • DWI b1000 32 directions and b3000 64 directions.
Diagnostic test: Blood sampling (serum/plasma preparation)
Blood will be screened for genetic modifications. Serum will be analyzed for auto-antibodies and other inflammatory and neurodegenerative biomarkers.
Diagnostic test: Cerebrospinal fluid (CSF)
CSF will be analyzed for inflammatory and neurodegenerative biomarkers.
Diagnostic test: Clinical assessments / questionnaires
  • Glasgow Outcome Scale Extended (functional outcome)
  • Short-Form 36 (quality of life),
  • EQ-5D (quality of life),
  • Mini-Mental State Extended (MMSE) (mental state assessment).
  • Barthel Index (daily living disabilities),
  • Montgomery-Åsberg Depression Score (MADRS-S) (level of depression)
  • Fatigue Severity Scale (FSS) (level of fatigue)

Other than that, neurological assessments focusing on the Unified Parkinson's Disease Rating Scale (UPDRS) will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GOSE vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
Barthel Index vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
Fatigue Severity Scale vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
MOCA vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
SF-36 vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
EQ-5D vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
MADRS vs structural outcome
Time Frame: 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).
Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs proteomic markers in serum
Time Frame: 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)).
Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs proteomic markers in cerebrospinal fluid
Time Frame: 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)).
Assessed at the chronic time-point (10-15 years after injury).
Structural outcome vs auto-antibodies in serum
Time Frame: 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)
Assessed at the chronic time-point (10-15 years after injury).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute vs chronic comparisons of proteomic markers in serum
Time Frame: 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).
From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
Acute vs chronic comparisons of proteomic markers in CSF
Time Frame: 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).
From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
Acute vs chronic comparisons of autoantibodies
Time Frame: 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)
From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)

Collaborators and Investigators

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

Sponsor

Karolinska University Hospital

Collaborators

Karolinska Institutet

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)

October 1, 2021

Primary Completion (ANTICIPATED)

January 31, 2023

Study Completion (ANTICIPATED)

January 31, 2025

Study Registration Dates

First Submitted

August 24, 2021

First Submitted That Met QC Criteria

February 1, 2022

First Posted (ACTUAL)

February 11, 2022

Study Record Updates

Last Update Posted (ACTUAL)

February 11, 2022

Last Update Submitted That Met QC Criteria

February 1, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-02010
  • 4-1857 /2021 (OTHER: Karolinska Institutet)
  • K 2021-5631 (OTHER: Karolinska University Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to local laws and regulations, we will not be able to share IPD.

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.

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