Long-term Follow-up in Severe Traumatic Brain Injury

NCT05235802 | Unknown

• 3 other identifiers: 2021-020104-1857 /2021K 2021-5631
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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).

Conditions

Traumatic Brain Injury; Neurodegenerative Diseases; Chronic Traumatic Encephalopathy

Keywords

Fluid biomarkers; Neuroinflammatory process; Auto-immunity; Structural imaging; Clinical assessment; Long-term follow-up

Outcome Measures

Primary Outcomes (10)

• 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).

• 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).

• 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).

• 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).

• 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).

• 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).

• 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).

• 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).

• 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).

• 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 Outcomes (3)

• 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)

• 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)

• 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)

Study Arms (1)

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); Diagnostic Test: Blood sampling (serum/plasma preparation); Diagnostic Test: Cerebrospinal fluid (CSF); Diagnostic Test: Clinical assessments / questionnaires

Interventions

Magnetic Resonance Imaging (MRI) (including functional MRI) DIAGNOSTIC_TEST

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.

Patients with traumatic brain injury about 10 years ago

Blood sampling (serum/plasma preparation) DIAGNOSTIC_TEST

Blood will be screened for genetic modifications. Serum will be analyzed for auto-antibodies and other inflammatory and neurodegenerative biomarkers.

Patients with traumatic brain injury about 10 years ago

Cerebrospinal fluid (CSF) DIAGNOSTIC_TEST

CSF will be analyzed for inflammatory and neurodegenerative biomarkers.

Patients with traumatic brain injury about 10 years ago

Clinical assessments / questionnaires DIAGNOSTIC_TEST

* 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.

Patients with traumatic brain injury about 10 years ago

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• \- Pregnancy

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, 17164, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid, blood (whole blood, serum and plasma).

MeSH Terms

Conditions

Brain Injuries, Traumatic; Neurodegenerative Diseases; Chronic Traumatic Encephalopathy

Interventions

Magnetic Resonance Imaging; Blood Specimen Collection; Cerebrospinal Fluid Pressure

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Injury, Chronic; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Eric P Thelin, MD, PhD

CONTACT

0046724654531; eric.thelin@ki.se

Susanna Friberg, MD

CONTACT

susanna.friberg@sll.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator (MD, PhD), Associate Professor

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: February 11, 2022
• Study Start: October 1, 2021
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2025
• Last Updated: February 11, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)