Microvascular Injury and Blood-brain Barrier Dysfunction as Novel Biomarkers and Targets for Treatment in Traumatic Brain Injury
2019年2月5日 更新者：David Clarke、Nova Scotia Health Authority
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.
研究概览
研究类型
观察性的
注册 (预期的)
120
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Nova Scotia
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Halifax、Nova Scotia、加拿大、B3H 3A7
- 招聘中
- Halifax Infirmary
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接触：
- David B. Clarke, MDCM, PhD, FRCSC, DABNS, FACS
- 电话号码：902-473-4591
- 邮箱：d.clarke@dal.ca
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 85年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
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).
描述
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)
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 观测模型：队列
- 时间观点：预期
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in brain volume with blood brain barrier dysfunction
大体时间：At < 4, 10 ± 2, and 90 ± 10 days post-injury
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Measurement of change in brain volume with BBBD and extent of permeability change as measured by DCE-MRI
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At < 4, 10 ± 2, and 90 ± 10 days post-injury
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Change in serum biomarkers of blood brain barrier dysfunction
大体时间：At < 4, 10 ± 2, and 90 ± 10 days post-injury
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Measurement of change in serum biomarkers of BBBD / neural injury (vWF, BDNF, GFAP, S100β, sTau, and sNFL)
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At < 4, 10 ± 2, and 90 ± 10 days post-injury
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Change in Glasgow Outcome Scale-Extended (GOS-E)
大体时间：At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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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.
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At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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Change in Rivermead Post Concussion Symptom Questionnaire (RPSQ)
大体时间：At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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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.
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At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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Change in Patient-Reported Outcomes Measurement Information System (PROMIS)
大体时间：At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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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.
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At 10 ± 2 days, 90 ± 10 days, and 1 year post-injury
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Change in post-traumatic epilepsy
大体时间：At 10 ± 2 days, 90 ± 10 days, 1 year, and 2 years post-injury
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Screening for post-traumatic epilepsy
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At 10 ± 2 days, 90 ± 10 days, 1 year, and 2 years post-injury
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：David B. Clarke, MD, PhD、Nova Scotia Health Authority
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年8月3日
初级完成 (预期的)
2019年8月3日
研究完成 (预期的)
2020年8月3日
研究注册日期
首次提交
2017年4月26日
首先提交符合 QC 标准的
2017年5月1日
首次发布 (实际的)
2017年5月4日
研究记录更新
最后更新发布 (实际的)
2019年2月6日
上次提交的符合 QC 标准的更新
2019年2月5日
最后验证
2019年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.