Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Change in CVR prior to sildenafil administration
研究概览
简要总结
The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women, aged ≥18
- •CT evidence of TBI-linked abnormality
- •Traumatic subarachnoid hemorrhage
- •Intracerebral hemorrhage/contusion
- •Subdural/epidural hematoma
- •Ability to undergo fNIRS testing with hypercapnia challenge
- •Subject able to provide informed consent
- •Attending of record agrees to include subject in study
排除标准
- •Unstable respiratory or hemodynamic status
- •Evidence of penetrating brain injury
- •TBI requiring craniotomy or craniectomy
- •Evidence or risk of ICP crisis
- •History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results)
- •History of pre-existing disabling mental illness (e.g. major depression or schizophrenia)
- •Exclusion criteria for sildenafil administration:
- •History of melanoma
- •current use of organic nitrate vasodilators
- •current use of ritonavir (HIV-protease inhibitor)
- •current use of erythromycin, ketoconazole, or itraconazole; current use of cimetidine
- •current use of alpha-blockers such as doxazosin (Cardura), tamsulosin (Flomax), and terazosin (Hytrin) prazosin (Minipres)
- •resting hypotension (systolic BP <90)
- •severe renal insufficiency
- •hepatic cirrhosis
- •acute ischemic stroke within past 2 months
- •acute myocardial infarction within past 2 months
- •unstable angina pectoris
- •acute or chronic heart failure
- •retinitis pigmentosa
- •pregnant or breastfeeding female
- •known hypersensitivity or allergy to sildenafil
- •Unstable cardiac status that constitutes a contraindication to sexual activity
- •Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data)
- •Nursing mothers
研究组 & 干预措施
Acute TBI
Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury.
干预措施: Sildenafil citrate (Drug)
Acute TBI
Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury.
干预措施: Functional Near Infared Spectroscopy (Device)
Acute TBI
Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury.
干预措施: Hypercapnia Challenge (Other)
Sub-acute/Chronic TBI
Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point.
干预措施: Sildenafil citrate (Drug)
Sub-acute/Chronic TBI
Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point.
干预措施: Functional Near Infared Spectroscopy (Device)
Sub-acute/Chronic TBI
Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point.
干预措施: Hypercapnia Challenge (Other)
Healthy Controls
The investigators will also enroll healthy "peer controls". These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit.
干预措施: Sildenafil citrate (Drug)
Healthy Controls
The investigators will also enroll healthy "peer controls". These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit.
干预措施: Functional Near Infared Spectroscopy (Device)
Healthy Controls
The investigators will also enroll healthy "peer controls". These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit.
干预措施: Hypercapnia Challenge (Other)
结局指标
主要结局
Change in CVR prior to sildenafil administration
时间窗: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
次要结局
- Change CVR after sildenafil administration(<72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years)
- Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI).(< 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years)
研究者
Ramon Diaz-Arrastia
Presidential Professor
University of Pennsylvania