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Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury (NK1)

Primary Purpose

Traumatic Brain Injury

Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Fosaprepitant
Sponsored by
Arun Gupta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Traumatic Brain Injury

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Other

    Arm Label

    Treatment

    Arm Description

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

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    Improvement in brain tissue oxygen tension
    Brain Tissue Oxygen will be measured continuously for up to 5 days after intervention
    Improvement in lactate/pyruvate ratio on microdialysis monitoring
    Microdialysis will be measured continuously for up to 5 days after intervention

    Full Information

    First Posted
    January 21, 2017
    Last Updated
    October 31, 2022
    Sponsor
    Arun Gupta
    Collaborators
    Cambridge University Hospitals NHS Foundation Trust
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03035838
    Brief Title
    Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
    Acronym
    NK1
    Official Title
    Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2022
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Alternate study commenced using different drug
    Study Start Date
    November 2021 (Anticipated)
    Primary Completion Date
    December 2022 (Anticipated)
    Study Completion Date
    April 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Arun Gupta
    Collaborators
    Cambridge University Hospitals NHS Foundation Trust

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    Detailed Description
    All severe traumatic brain injury patients admitted to the Cambridge University Hospital's Neurosciences Critical Care Unit who require insertion of a triple bolt for multimodal neuromonitoring (intracranial pressure-ICP, microdialysis-MD and brain tissue oxygen partial pressure-PbtO2) will be screened for participation in this study. Eligible patients will have an initial MRI scan in the first 24 hours from injury. Following this, and 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. Patients will then have a follow up MRI scan in the 24 hour following IVAMEND administration. Continuous ICP and PbtO2 monitoring as well as hourly microdialysis sampling will start immediately following insertion of monitors and at least 6 hours before and will continue for at least 12 hours after IVAMEND administration. ICP will continue to be monitored continuously in the 5 days following administration of IVAMEND. Microdialysis samples collected over the period of 6 hours before and 12 hours after the administration of Fosaprepitant will be stored and consequently used to measure the concentration of Substance P, nitric oxide (NO) and inflammatory cytokines.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Traumatic Brain Injury

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment
    Arm Type
    Other
    Arm Description
    There is only one arm in this study. Intracranial pressure and brain swelling will be monitored before and after administration of fosaprepitant
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Reduction in intracranial pressure
    Description
    Intracranial pressure will be measured continuously for up to 5 days after intervention
    Time Frame
    up to 5 days
    Secondary Outcome Measure Information:
    Title
    Improvement in brain tissue oxygen tension
    Description
    Brain Tissue Oxygen will be measured continuously for up to 5 days after intervention
    Time Frame
    up to 5 days
    Title
    Improvement in lactate/pyruvate ratio on microdialysis monitoring
    Description
    Microdialysis will be measured continuously for up to 5 days after intervention
    Time Frame
    up to 5 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Arun Gupta, MD PhD
    Organizational Affiliation
    Cambridge University Hospitals NHS Foundation Trust
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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