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Completed

NCT Number: NCT03139682

Microvascular Injury and Blood-brain Barrier Dysfunction as Novel Biomarkers and Targets for Treatment in Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability around the world. The social and economic burden of TBI is tremendous and the cost of TBI is estimated at $1 billion per year in Canada- $650 million in care and $580 million in lost productivity. Novel interventions aimed at TBI-linked molecular targets have been successful in limiting injury and improving neurologic recovery in animal models, thus providing compelling evidence that effective intervention is possible after injury. This study proposes to investigate traumatic microvascular injury (TMI) and specifically blood-brain barrier dysfunction (BBBD) as a candidate biomarker and therapeutic target in TBI.

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Key information

Conditions

Traumatic Brain Injury Blood Brain Barrier Defect Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Craniocerebral Trauma Nervous System Diseases Trauma, Nervous System Wounds and Injuries

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Halifax Infirmary

Halifax, Nova Scotia, B3H 3A7, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 - 85 inclusive
  • Clinically diagnosed TBI or evidence of TBI
  • For mild TBI, as defined by the American Congress on Rehabilitation Medicine (1993), clear evidence and/or documentation of blunt head injury and any one of the following:
  • any loss of consciousness up to 30 min
  • any loss of memory for events immediately before or after the injury as much as 24 h
  • any alteration of mental state at the time of the injury
  • focal neurologic deficits that might or might not be transient

but where the severity of the injury does not exceed oss of consciousness exceeding 30 min, posttraumatic amnesia longer than 24 h, a Glasgow Coma Scale score falling below 13 after 30 min.

  • For moderate TBI (GCS 9-12) and severe TBI (GCS 4-8) CT evidence of TBI-linked abnormality (intracranial lesion including traumatic SAH, contusion, extra-axial hematoma). For patients who are intubated, use best documented GCS within first 48 hours of injury.
  • Stable respiratory or hemodynamic status allowing MRI within 2-4 days of TBI as determined by the attending physician
  • Patient or substitute decision maker can provide consent

Exclusion criteria

  • Pre-existing known neurologic, psychiatric disease (dementia, prior severe TBI, schizophrenia, uncontrolled epilepsy, major depressive disorder, stroke, multiple sclerosis, brain tumor)
  • Serious infection, complications (sepsis, multilobe pneumonia, etc.) < 4 days after TBI
  • Acute ischemic heart disease (MI or unstable angina)
  • SBP < 100 mm Hg, DBP < 60 mm Hg
  • MRI contraindications; patient has metal implant, pacemaker, biostimulator, neurostimulator, internal defibrillator, history of metal in eye, inner ear implant, cerebral aneurism clip, joint replacement, any known metal in their body, or are pregnant or breast feeding
  • History or evidence of active malignancy
  • History or evidence of serious kidney (GFR =<60) , heart, or liver disease
  • Pregnant or breast-feeding women
  • Inability to complete follow up visits (e.g. tourists)

Treatment and study plan

Primary outcomes

  1. Change in brain volume with blood brain barrier dysfunction

    Time frame: At < 4, 10 ± 2, and 90 ± 10 days post-injury

    Measurement of change in brain volume with BBBD and extent of permeability change as measured by DCE-MRI

  2. Change in serum biomarkers of blood brain barrier dysfunction

    Time frame: At < 4, 10 ± 2, and 90 ± 10 days post-injury

    Measurement of change in serum biomarkers of BBBD / neural injury (vWF, BDNF, GFAP, S100β, sTau, and sNFL)

  3. Change in Glasgow Outcome Scale-Extended (GOS-E)

    Time frame: At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury

    The GOS-E is intended to provide a general index of overall outcome that is sensitive to small but clinically relevant treatment effects in people who sustain TBI.

  4. Change in Rivermead Post Concussion Symptom Questionnaire (RPSQ)

    Time frame: At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury

    The RPSQ is a 16-item self-report measure administered to individual(s) who sustained a TBI in order to measure the severity of symptoms and assess progress.

  5. Change in Patient-Reported Outcomes Measurement Information System (PROMIS)

    Time frame: At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury

    PROMIS is a set of person-centered measures that evaluates and monitors domains such as physical, mental and social health in adults and children. For this study, we will utilize the following domains: depression, fatigue, and pain interference.

  6. Change in post-traumatic epilepsy

    Time frame: At 10 ± 2 days, 90 ± 10 days, 1 year, and 2 years post-injury

    Screening for post-traumatic epilepsy

Sponsors and collaborators

Lead sponsor

Nova Scotia Health Authority

Other

Registry information

Important dates

Study start
2017
Primary completion
2019
Study completion
2021
First posted
May 4, 2017
Registry last updated
Feb 2, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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