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Withdrawn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
About this trial
This is an interventional basic science trial for Traumatic Brain Injury
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
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
NCT ID
NCT03035838
First Posted
January 21, 2017
Last Updated
October 31, 2022
Sponsor
Arun Gupta
Collaborators
Cambridge University Hospitals NHS Foundation Trust
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Withdrawn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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