Clinical trial NCT02990078: Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury
Official title: Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: TBI
Keywords: TBI
CVR
Hypercapnia
fNIRS
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2016-12-12
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female, aged 18 or older, presenting with a diagnosis of traumatic brain injury (TBI) and healthy peer control volunteers .

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in CVR prior to sildenafil administration
timeFrame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Secondary outcomes:
measure: Change CVR after sildenafil administration
timeFrame: <72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
measure: Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI).
timeFrame: < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania Perelman School of Medicine, Department of Neurology
name: Ramon Diaz-Arrastia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: