Long-term Follow-up in Severe Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— LONG-TBI  

Official title:

Long-term Follow-up in Severe Traumatic Brain Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05235802
• Other study ID #: 2021-02010
• Secondary ID: 4-1857 /2021K 20
• Status: Recruiting
• Start date: October 1, 2021
• Est. completion date: January 31, 2025

Study information

• Verified date: February 2022
• Source: Karolinska University Hospital
• Contact: Eric P Thelin, MD, PhD
• Phone: 0046724654531
• Email: eric.thelin[@]ki.se
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Injuries
• Brain Injuries, Traumatic
• Chronic Traumatic Encephalopathy
• Neurodegenerative Diseases
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

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.
• 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.
• Cerebrospinal fluid (CSF)
CSF will be analyzed for inflammatory and neurodegenerative biomarkers.
• 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.

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska University Hospital	Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GOSE vs structural outcome	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).
Primary	Barthel Index vs structural outcome	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).
Primary	Fatigue Severity Scale vs structural outcome	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).
Primary	MOCA vs structural outcome	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).
Primary	SF-36 vs structural outcome	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).
Primary	EQ-5D vs structural outcome	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).
Primary	MADRS vs structural outcome	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).
Primary	Structural outcome vs proteomic markers in serum	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).
Primary	Structural outcome vs proteomic markers in cerebrospinal fluid	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).
Primary	Structural outcome vs auto-antibodies in serum	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	Acute vs chronic comparisons of proteomic markers in serum	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)
Secondary	Acute vs chronic comparisons of proteomic markers in CSF	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)
Secondary	Acute vs chronic comparisons of autoantibodies	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)