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Trial record 44 of 317 for:    Recruiting, Not yet recruiting, Available Studies | "Brain Injuries, Traumatic"

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 : October 11, 2018
Sponsor:
Collaborator:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Arun Gupta, University of Cambridge

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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Fosaprepitant Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Reduction in intracranial pressure [ Time Frame: up to 5 days ]
    Intracranial pressure will be measured continuously for up to 5 days after intervention


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03035838


Contacts
Contact: Arun Gupta, MD PhD 07801231016 arun.gupta@addenbrookes.nhs.uk
Contact: Tamara Tajsic, MD PhD 07950194743 ttajsic@doctors.org.uk

Sponsors and Collaborators
Arun Gupta
Cambridge University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Arun Gupta, MD PhD Cambridge University Hospitals NHS Foundation Trust

Responsible Party: Arun Gupta, Principal Investigator, University of Cambridge
ClinicalTrials.gov Identifier: NCT03035838     History of Changes
Other Study ID Numbers: 212176
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Brain Injuries, Traumatic
Wounds and Injuries
Brain Injuries
Intracranial Hypertension
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Fosaprepitant
Aprepitant
Substance P
Neurokinin A
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action