Long-term Recovery and Microbiota-Gut-Brain Axis Disruption After Traumatic Brain Injury

Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorTurku University Hospital

About this trial

The OVERCOME-TBI project aims to collect multimodal data approximately 1-4 and 11-14 years after an earlier well-documented traumatic brain injury (TBI) and examine factors that influence disease progression in order to gain new scientific insights into the long-term pathophysiology of TBI and identify new therapeutic targets.

TBIs are among the most serious health problems worldwide and represents a significant burden for the injured, their families and society. It is estimated that more than 50 million people in the world suffer a TBI every year and half of all people will suffer a TBI in their lifetime. TBI diagnostics has lagged significantly behind that of many other diseases. The current methods for assessing severity and predicting outcomes are based only on initial stage variables, and there are no objective tools for monitoring disease progression. The current acute severity indices have shown only a modest association with outcome, particularly in patients with mTBI. However, even in patients with moderate-severe TBI, clinical predictors and imaging together explain only 35% of the variance in outcomes.

In the OVERCOME-TBI project, patients with a history of TBI sustained 1-4 and 11-14 years earlier will undergo extensive neurological, biochemical, microbiological, gastroenterological and imaging examinations. The patients have previously participated in the prospective studies of our research group, so that data on acute injuries, blood-based biomarkers and advanced imaging results are already available. The results are expected to yield objective diagnostic and treatment methods for the diagnosis of progressive brain disease after brain injury and for the identification of microbiome-gut-brain axis dysfunction associated with disease progression.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

All those who are alive and give their consent will be included from our previous prospective studies (TBIcare or PACoS-TBI)

Disqualifiers

For patients with TBI there are no exclusion criteria, and all eligible patients who give consent will be recruited

Those patients and controls with contraindication for head MRI (MRI-incompatible heart pacemaker, weight over 200 kg, mechanical heart valve prosthesis, first trimester of pregnancy, orbital area tattoo) will not undergo head MRI. Instead, they we will undergo the other assessments

For controls, those who have suffered a TBI or any other brain disorder after the TBIcare or PACoS-TBI study will be excluded.

Diagnosis of IBD or other diagnosis besides IBS causing severe GI symptoms, such as microscopic colitis or bile acid diarrhea

Trial population

All those who are alive and give their consent will be included from our previous prospective studies (TBIcare or PACoS-TBI)

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

  • blood-based protein biomarker assessments

    Diagnostic test

    Assessment of multiple blood-based biomarkers of different cellular origin and inflammatory mediators

  • blood-based metabolomic/lipidomic biomarker assessments

    Diagnostic test

    Assessment of multiple blood-based TBI-related metabolomic and lipidomic biomarkers

  • Diffusion-weighted magnetic resonance imaging (brain)

    Diagnostic test

    Diffusion-weighted magnetic resonance imaging

  • Structural magnetic resonance imaging (brain)

    Diagnostic test

    Structural magnetic resonance imaging

  • PET imaging (brain)

    Diagnostic test

    Positron emission tomography imaging

  • Standard colonoscopy with pinch biopsies

    Procedure/Surgery

    Standard colonoscopy including pinch biopsies from the bowel wall at several levels (terminal ileum, ascending colon, transverse colon, descending colon, and rectosigmoideum) for histology, microbiome analysis and metabolomics

  • Fecal microbiome assessments

    Diagnostic test

    Fecal microbiome assessments (DNA)

Treatment groups

160 Participants
are divided into 2 treatment groups
Group A: Patients with history of sustained traumatic brain injury7 interventions
Group B: Control patients with history of orthopedic injury without traumatic brain injury7 interventions

Trial outcomes

Primary outcomes

1

Biochemical neuroinflammation burden (lipids and metabolites)

Neuroinflammation burden as measured by levels of blood-based lipid biomarkers choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines, and sphingomyelins), branched-chain amino acids and medium-chain fatty acids

Time frame
1-14 years after traumatic brain injury
2

Biochemical neuroinflammation burden (cytokines)

Neuroinflammation burden as measured by levels of blood-based cytokines IL-6, IL-15, and MCP-1

Time frame
1-14 years after traumatic brain injury
3

Functional outcome

Functional outcome measured with Glasgow Outcome Scale Extended (GOSE, 1=dead - 8=complete recovery)

Time frame
1-14 years after traumatic brain injury
4

Changes in microbiota

DNA from fecal microbiome assessed by deep shot gun metagenomics approach, referenced to a population of healthy control subjects

Time frame
1-14 years after traumatic brain injury

Secondary outcomes

1

Changes in brain white and grey matter microstructure

Changes in brain white and grey matter microstructure as measured with diffusion tensor metrics

Time frame
1-14 years after traumatic brain injury
2

Accelerated brain ageing

Accelerated brain ageing calculated at a whole brain level using T1-weighted images and at a voxel-based level as the annualised Jacobian determinants in white matter and grey matter, referenced to a population of healthy control subjects

Time frame
1-14 years after traumatic brain injury

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Turku University Hospital

Lead sponsor

Aalto University

Collaborator

University of Geneva, Switzerland

Collaborator

Göteborg University

Collaborator

University of Cambridge

Collaborator

Örebro University, Sweden

Collaborator

University of Turku

Collaborator

This trial is not recruiting at the moment. You can still explore other options: