Brief Summary

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.

Conditions

• Traumatic Brain Injury

Intervention / Treatment

• Diagnostic Test: blood-based protein biomarker assessments
• Diagnostic Test: blood-based metabolomic/lipidomic biomarker assessments
• Diagnostic Test: Diffusion-weighted magnetic resonance imaging (brain)
• Diagnostic Test: Structural magnetic resonance imaging (brain)
• Diagnostic Test: PET imaging (brain)
• Procedure: Standard colonoscopy with pinch biopsies
• Diagnostic Test: Fecal microbiome assessments

Primary Outcome Measures

• Biochemical neuroinflammation burden (lipids and metabolites) (1-14 years after traumatic brain injury)
  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) (1-14 years after traumatic brain injury)
  Neuroinflammation burden as measured by levels of blood-based cytokines IL-6, IL-15, and MCP-1
• Functional outcome (1-14 years after traumatic brain injury)
  Functional outcome measured with Glasgow Outcome Scale Extended (GOSE, 1=dead - 8=complete recovery)
• Changes in microbiota (1-14 years after traumatic brain injury)
  DNA from fecal microbiome assessed by deep shot gun metagenomics approach, referenced to a population of healthy control subjects
• Inflammation burden on head positron emission tomography (1-14 years after traumatic brain injury)
  Neuroinflammation measured using the \[11C\]PK11195 radioligand

Study Officials

• Jussi P. Posti, MD, PhD (Principal Investigator) — Turku University Hospital and University of Turku