Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
Status:
Unknown status
Trial end date:
2021-04-01
Target enrollment:
Participant gender:
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
Details
Lead Sponsor:
Arun Gupta
Collaborator:
Cambridge University Hospitals NHS Foundation Trust