Inhaled Nitric Oxide for Treatment of Microvascular Dysfunction in Traumatic Brain Injury
Abstract
Background: Traumatic brain injury is a devastating condition that afflicted 320,000 troops from military operations in the last two decades. Additionally, it affects 1.5 million people in the general American public. Despite thirty years of animal model research on various medications to treat traumatic brain injury, development of medications to treat it has been slow and ineffective. A major damage caused by traumatic brain injury is due to lack of sufficient blood flow in numerous regions of the brain that happens shortly after the initial impact. In this proposal, we suggest using inhaled nitric oxide in traumatic brain injury given that it can selectively dilate blood vessels in the brain that has reduced blood flow. It also has been shown to reduce damaging effects such as inflammation and chemical stress. Focus Area: This proposal for a Research Level I Clinical Trial Award will address Focus Area 3: Treat, focusing on an intervention administered acutely, using personalized medicine approaches by tailoring treatments to biological elements present. By optimizing brain blood flow after traumatic brain injury using the innovative inhaled nitric oxide therapy, we hope to mitigate brain injury and improve outcomes. Objective and Rationale: The objective of this study is to show that inhaled nitric oxide can improve blood flow in the brain and brain metabolism after traumatic brain injury, attenuating brain injury and resulting in improved long-term function. The rationale for this study is the abundance of animal model evidence that nitric oxide is helpful in reducing injury in traumatic brain injury and the evidence of its safety seen in current clinical use. Also, inhaled nitric oxide is a safe agent approved by the Food and Drug Administration, used in newborn babies for lung diseases since the year 2000. It has also been used in clinical trials for adults, and it is actively being tested in other clinical trials currently. In this study, we will use a spectroscopy device that sends light waves through the skull in order to detect blood flow and oxygen use in the brain tissue. This device has been validated by our group previously in several studies 63, 66. We will also monitor the levels of specific proteins that increase with severity of the injury in order to see if inhaled nitric oxide lowers their levels by reducing injury. CBPR Approach: We will work in partnership with a TBI-survivor and an active member of a local community who will serve as a Lived Experience Consultant (LEC). Semi-annual meetings will be held to discuss the recruitment process, data analysis, and eventual dissemination of information at the end of the study. Problem to be Addressed, Applicability, and Impact: We will optimize blood flow in the brain after traumatic brain injury by administering inhaled nitric oxide for the first three hours after injury. We are aiming to show that this is both a safe treatment and effective in reducing brain injury. As this agent is in current clinical use and there is a well demonstrated side effect profile, clinicians would be able to administer this agent with much ease if therapeutic potential can be demonstrated. Without the potential regulatory barriers that novel pharmacological agents would have to undergo and delays that would take place to build a new manufacturing infrastructure, inhaled nitric oxide is rapidly applicable to the traumatic brain injury patients. If the current trial can show that it is safe and effective treatment for TBI, it would have an enormous impact in the clinical outcomes of these patients given there are currently no treatment regimen that can limit secondary injury after TBI. Since the blood flow improvement may lead to functional improvements weeks to months after the treatment, patient-related outcome may potentially show up at 6-month assessment period. Benefit to the Military: The findings of study can directly benefit the military
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310852
Entities
People
- Ramon Diaz-Arrastia
Organizations
- United States Army
- University of Pennsylvania