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

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

Interventions

DIAGNOSTIC_TEST

blood-based protein biomarker assessments

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

DIAGNOSTIC_TEST

blood-based metabolomic/lipidomic biomarker assessments

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

DIAGNOSTIC_TEST

Diffusion-weighted magnetic resonance imaging (brain)

Diffusion-weighted magnetic resonance imaging

DIAGNOSTIC_TEST

Structural magnetic resonance imaging (brain)

Structural magnetic resonance imaging

DIAGNOSTIC_TEST

PET imaging (brain)

Positron emission tomography imaging

PROCEDURE

Standard colonoscopy with pinch biopsies

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

DIAGNOSTIC_TEST

Fecal microbiome assessments

Fecal microbiome assessments (DNA)

Sponsors & Collaborators

• Aalto University

  collaborator OTHER

• University of Geneva, Switzerland

  collaborator OTHER

• Göteborg University

  collaborator OTHER

• University of Cambridge

  collaborator OTHER

• Örebro University, Sweden

  collaborator OTHER

• University of Turku

  collaborator OTHER

• Turku University Hospital

  lead OTHER_GOV

Principal Investigators

• Jussi P. Posti, MD, PhD · Turku University Hospital and University of Turku

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-01

Primary Completion

2027-12-31

Completion

2028-12-31