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

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ClinicalTrials.gov Identifier: NCT03035838
Recruitment Status : Not yet recruiting
First Posted : January 30, 2017
Last Update Posted : May 3, 2017
Sponsor:
Collaborator:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Arun Gupta, University of Cambridge

January 21, 2017
January 30, 2017
May 3, 2017
September 2017
December 2018   (Final data collection date for primary outcome measure)
Reduction in intracranial pressure [ Time Frame: up to 5 days ]
Intracranial pressure will be measured continuously for up to 5 days after intervention
Same as current
Complete list of historical versions of study NCT03035838 on ClinicalTrials.gov Archive Site
  • Improvement in brain tissue oxygen tension [ Time Frame: up to 5 days ]
    Brain Tissue Oxygen will be measured continuously for up to 5 days after intervention
  • Improvement in lactate/pyruvate ratio on microdialysis monitoring [ Time Frame: up to 5 days ]
    Microdialysis will be measured continuously for up to 5 days after intervention
Same as current
Not Provided
Not Provided
 
Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
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.
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.
Interventional
Early Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Traumatic Brain Injury
Drug: Fosaprepitant
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
There is only one arm in this study. Intracranial pressure and brain swelling will be monitored before and after administration of fosaprepitant
Intervention: Drug: Fosaprepitant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
15
Same as current
April 2019
December 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult, Older Adult)
No
Contact: Arun Gupta, MD PhD 07801231016 arun.gupta@addenbrookes.nhs.uk
Contact: Tamara Tajsic, MD PhD 07950194743 ttajsic@doctors.org.uk
Not Provided
 
 
NCT03035838
212176
Yes
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
Plan to Share IPD: No
Arun Gupta, University of Cambridge
Arun Gupta
Cambridge University Hospitals NHS Foundation Trust
Principal Investigator: Arun Gupta, MD PhD Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP