Cerebrovascular Reactivity Assessed With fNIRS as a Biomarker of TCVI After Acute Traumatic Brain Injury in Military

• Status: Unknown status
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The study includes people who have recently had a traumatic brain injury (TBI) and healthy controls who have not had a TBI and is designed to measure brain blood flow serially after a TBI. Studies have shown that small blood vessels in the brain may be injured during a TBI. The goal is to learn about brain blood vessel function from as early as the first week to 6 months after a TBI . The study uses Near Infrared Spectroscopy (NIRS) which uses small lights that detect oxygen levels in the blood, measuring blood flow in the brain. This is compared with magnetic resonance imaging (MRI). When blood flow increases in the brain in response to a stimulus, this is called cerebral vascular reactivity (CVR).

The study aims to learn about CVR using a few minutes of special breathing similar to breath holding while in an MRI (magnetic resonance imaging), and CVR measures after one dose of a common drug called sildenafil (generic Viagra) 50 mg taken once during CVR measurements at each of up to 4 visits. The investigators will measure CVR at different times during a 6-month period in participants who have had a TBI to see how CVR measures and blood vessels function during the first 6 months after a brain injury.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Uniformed Services University of the Health Sciences
• Collaborator: Walter Reed National Military Medical Center
• Treatments: Citric Acid; Sildenafil Citrate; Sodium Citrate

Criteria

Inclusion Criteria (See Table 2 for more details)

1. Age 18 to 55 years, inclusive

2. Either gender

3. TBI subjects ONLY: Meets DoD criteria for moderate or severe TBI and TBI occurred less than 30 days prior to study enrollment (Sustained a traumatically induced physiological disruption of brain function, as manifested by at least one of the following:

1. . Period of loss of consciousness > 30 minutes

2. . Loss of memory for events lasting> 24 hours after the accident

3. . Alteration of mental state lasting> 24 hours after the accident (e.g., feeling dazed, disoriented, and confused)

4. . Clinical neuroimaging intracranial abnormality.

• Traumatically induced includes the head being struck, the head striking an object, or the brain undergoing an acceleration/deceleration movement (i.e. whiplash) without direct external trauma to the head.

4. Ability to undergo fNIRS testing with hypercapnia challenge serially

5. Ability to provide informed consent.

Exclusion Criteria:

1. Unstable respiratory or hemodynamic status

2. Evidence of penetrating brain injury

3. TBI requiring craniotomy or craniectomy

4. 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

5. History of pre-existing disabling mental illness, e.g. major depression or schizophrenia

6. Exclusion criteria for sildenafil:

History of melanoma; Current use of organic nitrate vasodilators; 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 (Minipress); Resting hypotension (systolic BP <90); Severe renal insufficiency; Hepatic cirrhosis; Cardiac failure or coronary artery disease causing unstable angina; Retinitis pigmentosa; Pregnant or breastfeeding female; Known hypersensitivity or allergy to sildenafil.

7. Inability to read and communicate in English

8. Exclusion criterion for healthy subjects only: History of TBI.

9. Current use of a PDE5 inhibitor (a drug such as Sildenafil, Tadalafil, Vardenafil, Avanafil, Udenafil,Dipyridamole, Vardenafil hydrochloride)