Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury

TBI Clinical Trial

Official title:

Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02990078
• Other study ID #: 825942
• Status: Terminated
• Start date: December 2016
• Est. completion date: September 30, 2022

Study information

• Verified date: October 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: September 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• TBI

Intervention

Drug:
• Sildenafil 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.

Device:
• Functional 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.

Other:
• Hypercapnia 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.

Locations

Country	Name	City	State
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CVR prior to sildenafil administration		< 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Secondary	Change CVR after sildenafil administration		<72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years
Secondary	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