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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03139682
• Other study ID #: TMI_BBBD_2017
• Status: Completed
• Start date: August 3, 2017
• Est. completion date: August 3, 2021

Study information

• Verified date: January 2023
• Source: Nova Scotia Health Authority
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: August 3, 2021
• Est. primary completion date: August 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Blood Brain Barrier Defect
• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Locations

Country	Name	City	State
Canada	Halifax Infirmary	Halifax	Nova Scotia

Sponsors (1)

Lead Sponsor	Collaborator
Nova Scotia Health Authority

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in brain volume with blood brain barrier dysfunction	Measurement of change in brain volume with BBBD and extent of permeability change as measured by DCE-MRI	At < 4, 10 ± 2, and 90 ± 10 days post-injury
Primary	Change in serum biomarkers of blood brain barrier dysfunction	Measurement of change in serum biomarkers of BBBD / neural injury (vWF, BDNF, GFAP, S100ß, sTau, and sNFL)	At < 4, 10 ± 2, and 90 ± 10 days post-injury
Primary	Change in Glasgow Outcome Scale-Extended (GOS-E)	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.	At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
Primary	Change in Rivermead Post Concussion Symptom Questionnaire (RPSQ)	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.	At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
Primary	Change in Patient-Reported Outcomes Measurement Information System (PROMIS)	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.	At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
Primary	Change in post-traumatic epilepsy	Screening for post-traumatic epilepsy	At 10 ± 2 days, 90 ± 10 days, 1 year, and 2 years post-injury