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

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ClinicalTrials.gov Identifier: NCT03139682
Recruitment Status : Recruiting
First Posted : May 4, 2017
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
David Clarke, Nova Scotia Health Authority

Brief 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.

Condition or disease
Traumatic Brain Injury Blood Brain Barrier Defect

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Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Microvascular Injury and Blood-brain Barrier Dysfunction as Novel Biomarkers and Targets for Treatment in Traumatic Brain Injury
Actual Study Start Date : August 3, 2017
Estimated Primary Completion Date : August 3, 2019
Estimated Study Completion Date : August 3, 2020

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  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


Biospecimen Retention:   Samples Without DNA
Serum tau protein (sTau), von Willebrand factor (vWF), brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP),S100β, and serum neurofilament light (sNFL).


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
We will recruit mild (n=40), moderate (n=40) and severe (n=40) TBI patients with a TBI-linked abnormality (e.g. epidural & subdural hematomas, subarachnoid hemorrhage, contusions). TBI will be classified by severity using the Glasgow Coma Scale (GCS); mild TBI (GCS13-15), moderate TBI (GCS 9-12), and severe TBI (GCS <8).
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03139682


Contacts
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Contact: Lorelei Audas, BScN 902-473-2397 lorelei.audas@nshealth.ca
Contact: Tamara Mitterer, BScN 902-473-7883 tamara.mitterer@nshealth.ca

Locations
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Canada, Nova Scotia
Halifax Infirmary Recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Contact: David B. Clarke, MDCM, PhD, FRCSC, DABNS, FACS    902-473-4591    d.clarke@dal.ca   
Sponsors and Collaborators
Nova Scotia Health Authority
Investigators
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Principal Investigator: David B. Clarke, MD, PhD Nova Scotia Health Authority

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Responsible Party: David Clarke, Neurosurgeon, Nova Scotia Health Authority
ClinicalTrials.gov Identifier: NCT03139682     History of Changes
Other Study ID Numbers: TMI_BBBD_2017
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System