Traumatic Brain InjuryEarly Phase 1NK1NCT03035838
Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
A Early Phase 1 study testing Fosaprepitant in people with Traumatic Brain Injury, run by Arun Gupta.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Fosaprepitant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2021to Apr 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with traumatic brain injury requiring intracranial pressure monitoring
- Age 18-65 years
- Abnormal CT scan
Who cannot join
- 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
About this study
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.
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Fosaprepitant
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosaprepitantDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Other | There is only one arm in this study. Intracranial pressure and brain swelling will be monitored before and after administration of fosaprepitant Receives: Drug: Fosaprepitant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in intracranial pressure
Intracranial pressure will be measured continuously for up to 5 days after intervention
Measured: up to 5 days
Secondary outcomes (2)
Improvement in brain tissue oxygen tension
Brain Tissue Oxygen will be measured continuously for up to 5 days after intervention
Measured: up to 5 days
Improvement in lactate/pyruvate ratio on microdialysis monitoring
Microdialysis will be measured continuously for up to 5 days after intervention
Measured: up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2017 (estimated)
- Study startNov 2021 (estimated)
- Primary completionDec 2022 (estimated)
- Study completionApr 2023 (estimated)
Why it stopped: Alternate study commenced using different drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arun Gupta
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Arun Gupta, University of Cambridge
- Investigators
- Arun Gupta, MD PhD, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03035838
- Sponsor's protocol ID
- 212176
- Acronym
- NK1
- Status last verified
- Oct 2022
- First submitted
- 21 Jan 2017
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Importance of Substance P in Intracranial Pressure Elevation Following Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT03035838
- Acronym / sponsor ID
- NK1 / 212176
- Conditions
- Traumatic Brain Injury
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Alternate study commenced using different drug
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Arun GuptaUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Study start
- Nov 2021 (estimated)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 30 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Other | Drug: FosaprepitantThere is only one arm in this study. Intracranial pressure and brain swelling will be monitored before and after administration of fosaprepitant |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with traumatic brain injury requiring intracranial pressure monitoring
- Age 18-65 years
- Abnormal CT scan
Key exclusion criteria (7 listed)
- Bilateral fixed and dilated pupils
- Bleeding diathesis
- Devastating injuries; patient not expected to survive > 24 hours
- Brainstem damage
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FosaprepitantWithin 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. | Drug | Treatment |
Primary outcome
Reduction in intracranial pressure
Time frame: up to 5 days
Intracranial pressure will be measured continuously for up to 5 days after intervention
2 secondary outcomes
Improvement in brain tissue oxygen tension
Time frame: up to 5 days
Improvement in lactate/pyruvate ratio on microdialysis monitoring
Time frame: up to 5 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arun Gupta, MD PhD principal investigator
Cambridge University Hospitals NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fosaprepitant in people with Traumatic Brain Injury, run by Arun Gupta.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in intracranial pressure (time frame: up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2022.