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 volunteersQualifiers
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
Case-control
Prospective
Treatments tested in this trial
blood-based protein biomarker assessments
Diagnostic testAssessment of multiple blood-based biomarkers of different cellular origin and inflammatory mediators
blood-based metabolomic/lipidomic biomarker assessments
Diagnostic testAssessment of multiple blood-based TBI-related metabolomic and lipidomic biomarkers
Diffusion-weighted magnetic resonance imaging (brain)
Diagnostic testDiffusion-weighted magnetic resonance imaging
Structural magnetic resonance imaging (brain)
Diagnostic testStructural magnetic resonance imaging
PET imaging (brain)
Diagnostic testPositron emission tomography imaging
Standard colonoscopy with pinch biopsies
Procedure/SurgeryStandard 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 testFecal microbiome assessments (DNA)
Treatment groups
Trial outcomes
Primary outcomes
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
Biochemical neuroinflammation burden (cytokines)
Neuroinflammation burden as measured by levels of blood-based cytokines IL-6, IL-15, and MCP-1
Functional outcome
Functional outcome measured with Glasgow Outcome Scale Extended (GOSE, 1=dead - 8=complete recovery)
Changes in microbiota
DNA from fecal microbiome assessed by deep shot gun metagenomics approach, referenced to a population of healthy control subjects
Secondary outcomes
Changes in brain white and grey matter microstructure
Changes in brain white and grey matter microstructure as measured with diffusion tensor metrics
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
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
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