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

NCT03035838 | Withdrawn Early Phase 1 DMC

• 1 other identifier: 212176
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Reduction in intracranial pressure

  Intracranial pressure will be measured continuously for up to 5 days after intervention

  up to 5 days

Secondary Outcomes (2)

• Improvement in brain tissue oxygen tension

  up to 5 days

• Improvement in lactate/pyruvate ratio on microdialysis monitoring

  up to 5 days

Study Arms (1)

Treatment

OTHER

There is only one arm in this study. Intracranial pressure and brain swelling will be monitored before and after administration of fosaprepitant

Drug: Fosaprepitant

Interventions

Fosaprepitant DRUG

Within 24 hours from injury, IVAMEND (the intravenous formulation of the NK-1 antagonist fosaprepitant) will be administered at a dose of 300 mg, intravenously over 1 hour.

Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with traumatic brain injury requiring intracranial pressure monitoring
• Age 18-65 years
• Abnormal CT scan

You may not qualify if:

• 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

Sponsors & Collaborators

• Arun Gupta: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

fosaprepitant

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Arun Gupta, MD PhD

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 21, 2017
• First Posted: January 30, 2017
• Study Start: November 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: April 1, 2023
• Last Updated: November 3, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share