Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury

University of Pennsylvania26 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

TBI

Interventions

Sildenafil citrateDRUG

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.

Functional Near Infared SpectroscopyDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. 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 8. Unstable cardiac status that constitutes a contraindication to sexual activity 9. Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data) 10. Nursing mothers

Locations (1)

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Change in CVR prior to sildenafil administration

Time frame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years

Secondary Outcomes

Change CVR after sildenafil administration

Time frame: <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).

Time frame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years

Data from ClinicalTrials.gov

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