Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury

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

Summary

Traumatic brain (TBI) injury is the major cause of morbidity and mortality worldwide especially in population under 40 years of age and has a significant socioeconomic impact. TBI results from the head impacting with an object or from acceleration/deceleration forces that produce vigorous movement of the brain within the skull, with the resultant mechanical forces potentially damaging neurones and blood vessels and causing irreversible, primary brain injury. Primary injury leads to activation of cellular and molecular responses which lead to disruption of the blood-brain barrier causing the brain to swell. As the intracranial space is not expandable (i.e. is fixed), this swelling leads to increase in intracranial pressure (ICP) compromising blood supply to the rest of the brain leading to secondary brain injury. As we are unable to reverse the primary injury, current protocols use supportive measures to control the ICP and ensure optimal blood supply to the brain in an attempt to minimize secondary injury. Our understanding of the factors involved in the initiation and propagation of brain swelling in TBI is growing and the role of neuroinflammatory cytokines in this process is increasingly recognized. In preclinical models of TBI, a specific inflammatory cytokine termed substance P (SP) is found to be associated with blood-brain barrier disruption and development of brain oedema in the immediate phase following injury. The aim of this study is to examine the role of SP in the genesis of cerebral oedema and elevation of ICP and thus secondary injury following human TBI. This would be achieved by blocking SP function with a SP receptor antagonist Fosaprepitant (IVEMEND®, Merck) in the first 24 hours following TBI and then continuously measuring ICP and assessing the evolvement of TBI using magnetic resonance imaging.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Arun Gupta
• Collaborator: Cambridge University Hospitals NHS Foundation Trust
• Treatments: Aprepitant; Fosaprepitant; Neurokinin A; Substance P

Criteria

Inclusion Criteria:

• Patients with traumatic brain injury requiring intracranial pressure monitoring

• Age 18-65 years

• Abnormal CT scan

Exclusion Criteria:

• Bilateral fixed and dilated pupils

• Bleeding diathesis

• Devastating injuries; patient not expected to survive > 24 hours

• Brainstem damage

• Pregnancy

• Sedation with Midazolam

• Patients under 18 years of age