Traumatic Brain InjuryLONG-TBINCT05235802
Long-term Follow-up in Severe Traumatic Brain Injury
An observational study of Traumatic Brain Injury and Neurodegenerative Diseases, run by Karolinska University Hospital at 1 site in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury, Neurodegenerative Diseases, Chronic Traumatic Encephalopathy
- What is being tested?
- Magnetic Resonance Imaging (MRI) (including functional MRI), Blood sampling (serum/plasma preparation) and Cerebrospinal fluid (CSF)
- How many people
- 100 participants
- Where
- 1 siteSweden
- Study dates
- 1 Oct 2021to 31 Jan 2025
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Having suffered a traumatic brain injury and being treated at the Karolinska University Hospital between 2007 and 2015.
- Age >18 years of age
Who cannot join
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Susanna Friberg, MD contact
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital
Stockholm, 17164
Susanna Friberg, MD, susanna.friberg@regionstockholm.se
About this study
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.
Read more
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).
- Being tested
- Magnetic Resonance Imaging (MRI) (including functional MRI), Blood sampling (serum/plasma preparation), Cerebrospinal fluid (CSF), Clinical assessments / questionnaires
- Keywords
- Fluid biomarkers, Neuroinflammatory process, Auto-immunity, Structural imaging, Clinical assessment, Long-term follow-up
- Medical subject headings
- Brain Injuries, Traumatic, Neurodegenerative Diseases, Chronic Traumatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
Cerebrospinal fluid (CSF)Diagnostic test
CSF will be analyzed for inflammatory and neurodegenerative biomarkers.
Clinical assessments / questionnairesDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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)).
Measured: 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)).
Measured: 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)
Measured: Assessed at the chronic time-point (10-15 years after injury).
Secondary outcomes (3)
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).
Measured: 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
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).
Measured: 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
A panel of auto-antibodies targeting central nervous system antigens will be compared between the acute and chronic phase (comparison of antibody titers)
Measured: From samples acquired in the acute phase (first weeks after injury) with samples acquired in the chronic phase (10-15 years after injury)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2022
- Study start1 Oct 2021
- Primary completion31 Jan 2023 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Principal investigator, Eric Thelin, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05235802
- Sponsor's protocol ID
- 2021-02010
- Other IDs
- 4-1857 /2021, K 2021-5631
- Acronym
- LONG-TBI
- Status last verified
- Feb 2022
- First submitted
- 24 Aug 2021
- Last updated
- 11 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Due to local laws and regulations, we will not be able to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Follow-up in Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT05235802
- Acronym / sponsor ID
- LONG-TBI / 2021-02010
- Keywords
- Fluid biomarkers, Neuroinflammatory process, Auto-immunity, Structural imaging, Clinical assessment, Long-term follow-up
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 31 Jan 2023 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 11 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with traumatic brain injury about 10 years ago | – | 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 / questionnairesPatients that had suffered a TBI and being managed at the Neurosurgical Department at the Karolinska University Hospital between 2007 and 2015. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Having suffered a traumatic brain injury and being treated at the Karolinska University Hospital between 2007 and 2015.
- Age >18 years of age
Key exclusion criteria (1 listed)
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Patients with traumatic brain injury about 10 years ago |
| 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 | Patients with traumatic brain injury about 10 years ago |
| Cerebrospinal fluid (CSF)CSF will be analyzed for inflammatory and neurodegenerative biomarkers. | Diagnostic test | Patients with traumatic brain injury about 10 years ago |
| 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. | Diagnostic test | Patients with traumatic brain injury about 10 years ago |
Primary outcome
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).
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).
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).
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).
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).
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).
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).
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)).
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)).
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)
3 secondary outcomes
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)
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)
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Individual participant dataSharing planned: No. Due to local laws and regulations, we will not be able to share IPD.
Related trials for Traumatic Brain Injury
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanna Friberg, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury and Neurodegenerative Diseases, run by Karolinska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eric P Thelin, MD, PhD (0046724654531, eric.thelin@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GOSE vs structural outcome (time frame: Assessed at the chronic time-point (10-15 years after injury).). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2022.