TBI
Conditions
Keywords
TBI, CVR, Hypercapnia, fNIRS
Brief summary
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.
Interventions
DRUGSildenafil citrate
Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.
DEVICEFunctional Near Infared Spectroscopy
Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.
OTHERHypercapnia Challenge
The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.
Sponsors
University of Pennsylvania
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Men and women, aged ≥18 2. CT evidence of TBI-linked abnormality * Traumatic subarachnoid hemorrhage * Intracerebral hemorrhage/contusion * Subdural/epidural hematoma 3. Ability to undergo fNIRS testing with hypercapnia challenge 4. Subject able to provide informed consent 5. Attending of record agrees to include subject in study
Exclusion criteria
1. Unstable respiratory or hemodynamic status 2. Evidence of penetrating brain injury 3. TBI requiring craniotomy or craniectomy 4. Evidence or risk of ICP crisis 5. 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) 6. History of pre-existing disabling mental illness (e.g. major depression or schizophrenia) 7.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in CVR prior to sildenafil administration | < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed