Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
UNKNOWN
Total Enrollment
100 participants
Study Classification
OBSERVATIONAL
Study Start Date
2017-09-16
Study Completion Date
2022-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Head injury is a common and devastating condition that can affect people at any stage of their lives. The treatment of severe head injury takes place in intensive care where interventions are designed to protect the brain from further injury and provide the best environment for recovery. A number of different monitors are used after head injury, including a monitor called microdialysis, to measure how the brain is generating energy. Abnormalities in these monitors guide doctors to the right treatments when the brain is at risk of further injury. There are lots of ways that the brain can be injured further after head injury such as raised pressure in the skull from brain swelling, low oxygen levels and low glucose levels. In this study we aim to combine information from all of these monitors to figure out what the underlying problem is and choose the right intervention to treat the problem that is affecting the patient at the time and compare this with previous treatment protocols to see if it improved outcome.
Aim:
To establish and validate a protocol to treat abnormalities in a microdialysis measure called lactate/pyruvate ratio (LPR) that reflects how cells are generating energy, and compare it with patient cohorts not being monitored using the current protocol.
Aim:
To establish and validate a protocol to treat abnormalities in a microdialysis measure called lactate/pyruvate ratio (LPR) that reflects how cells are generating energy, and compare it with patient cohorts not being monitored using the current protocol.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Multimodal Approach to Testing the Acute Effects of Mild Traumatic Brain Injury (mTBI)
NCT02069613
Concussion, Mild
COMPLETED
A Study of Biomarkers of Mild Traumatic BRAIN Injury
NCT04032509
Mild Traumatic Brain Injury
COMPLETED
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
NCT04900168
Moderate Traumatic Brain Injury
UNKNOWN
Evaluating Near-infrared Spectroscopy Devices for Monitoring Traumatic Brain Injury
NCT07106216
Tramatic Brain Injury
NOT_YET_RECRUITING
The Role of MEG in Assessment and Diagnosis In mTBI
NCT03867513
Brain Injuries, Traumatic
UNKNOWN
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Background:
Traumatic brain injury (TBI, "head injury) is a major cause of morbidity and mortality worldwide (Hyder et al., 2007). During the first four decades of life, trauma is the leading cause of death and TBI is involved in at least half the number of cases (Jennett, 1996). In the UK, 1,500 per 100,000 of the population (total 1 million) attend Accident and Emergency Departments with a head injury per year. Of these, around 135,000 people are admitted each year and there are an estimated 500,000 people (aged 16 - 74) with long term disabilities as a direct result of TBI (Headway, 2016). Approximately 10 per 100,000 per year die from head injury (Jennett and MacMillan, 1981, Hutchinson et al., 1998).
The major determinant of outcome from TBI is the severity of the primary injury, which is irreversible. However, primary injury invariably leads to the activation of cellular and molecular cascades which mediate further secondary injury that evolve over the ensuing hours and days (Masel and DeWitt, 2010) and are therefore amenable to therapeutic intervention. These molecular cascades can lead to brain swelling within the confines of a fixed intracranial compartment, leading to increased intracranial pressure (ICP) and compromising cerebral perfusion pressure (CPP) (Werner and Engelhard, 2007). The control of ICP and maintenance of CPP has been the bedrock of neurointensive care management of TBI for several decades, however, a recent multicenter randomised clinical trial could not show a long-term favorable outcome with ICP guided therapy (Carney et al., 2012).
The Neuro Critical Care Unit (NCCU) in Cambridge is a world leader in TBI monitoring and routinely employs multi-modal monitoring comprising of ICP, brain tissue oxygen and microdialysis monitoring, in every TBI patient. Conceptually, microdialysis monitoring is an attractive method of assessing tissue biochemistry as it provides a direct measure of metabolic substrates at the cellular level at which energy failure occurs. Specifically, the microdialysis derived measure Lactate/Pyruvate Ratio (LPR) is a measure of cellular redox state and therefore the balance between aerobic and anaerobic metabolism. To date, studies in the literature have focused on demonstrating that individual monitoring parameters e.g. microdialysis derived LPR\>25 correlate with an unfavorable outcome in multivariate analyses (Sarrafzadeh et al., 2000, Timofeev et al., 2011).
One reason that an ICP monitoring trial has not been proven to deliver improved outcome is that there are several alternative routes to neuronal injury include insufficient oxygen delivery (Nortje and Gupta, 2006), diffusion barrier within tissues (Smielewski et al., 2002), tissue hypoglycaemia (Vespa et al., 2003) and mitochondrial dysfunction (Verweij et al., 2000). Our understanding of these pathophysiological mechanisms has been greatly advanced by the use of multi-modality monitoring including direct measurement of brain tissue oxygen and cerebral microdialysis. In theory, these pathophysiological states could be treated using treatment of ICP lowering therapy, augmenting cerebral perfusion pressure (CPP), increasing oxygen delivery and augmenting glucose delivery. Though, we currently don't know the best way to combine these treatments and they are often used together making independent analysis difficult. Moreover, there is currently no approved therapy for mitochondrial dysfunction, and while some claim that mitochondrial dysfunction is imminent in increased LPR (Nordstrom et al., 2016), the reality is more complex as there will be conditions that are treatable with an increased LPR, but these states need to be better established for clinicians in order to accurately guide treatment (Lazaridis and Robertson, 2016). Previous implementations of guidelines in TBI have shown to improve care and reduce health related cost, something we hope to achieve with our established clinical protocol (Faul et al., 2007).
Overall research design
We propose a treatment algorithm exploring how a standardised clinical protocol that incorporates multi-modality monitoring parameters (intracranial pressure, brain tissue oxygen and microdialysis parameters) can be systematically and rigorously applied in a traumatic brain injury (TBI) patient cohort with deranged brain chemistry (LPR \>25).
Our principal outcome metric is the ability for the protocol to improve the LPR, as well as to see how many patients that may be stratified into any of the suggest treatment categories (see below).
Interventions and assessments
Following inclusion, patients will be monitored using the standard clinical monitoring for sedated and ventilated TBI patients which includes an Intracranial Pressure (ICP) monitor device, a brain tissue oxygen monitor (PbO2) and microdialysis to assess brain biochemistry (Le Roux et al., 2014, Hutchinson et al., 2015). While ICP and PbO2 are measured continually, microdialysis samples are measured hourly. If a derangement in LPR is identified (LPR\>25), patients will have an increase in monitoring frequency to every 30 minutes. Our primary measure of deranged energy generation at the cellular level is a LPR\>25. This threshold has been shown to relate to an unfavourable long-term outcome (Timofeev et al., 2011, Stein et al., 2012). If the LPR\>25 on two consecutive samples (to avoid spurious or transient derangements) it will trigger specific treatment strategies depending on the other contemporaneous monitoring modalities. After each intervention, two consecutive microdialysis samples will be taken to confirm whether LPR has been corrected or whether a further step in the protocol needs to be taken. The sequence of interventions has been chosen on the basis of the strength of association of each intervention with LPR in the existing literature (Hutchinson et al., 2015).
STAGE 1: Correction of Intracranial Hypertension; ICP corrected to \<20mmHg Raised ICP compromises delivery of both substrate and oxygen to the injured brain, by reducing Cerebral Perfusion Pressure) and is in itself an independent predictor of poor outcome (Marmarou et al., 1991, Bratton et al., 2007b). In the acute setting we will use hypertonic saline (100ml 5% saline by central venous bolus) as a rapid means of reducing ICP (Marko, 2012). This will be followed by an escalation of ICP control measures using our established ICP protocol (Helmy et al., 2007).
STAGE 2: Ensure sufficient Oxygenation; increase PbO2\>15mmHg
Increased LPR can reflect ischaemia and in the first instance we will ensure that there is adequate oxygenation by increasing the PbO2\>15mmHg. This threshold of PbO2 has been recognised as physiological in the literature (van den Brink et al., 2000). There are two possible limitations to oxygen availability to brain tissue recognised in TBI:
1. Inadequate oxygen delivery (DO2(brain)=Cerebral Blood Flow (CBF) x Oxygen Capacity in Blood) Firstly, we will ensure adequate haemoglobin concentration (\>8g/dl) within the blood and normovolemia to ensure adequate oxygen carrying capacity. Cerebral perfusion pressure (CPP) is monitored as a surrogate of CBF and is usually maintained at around 60-80 mmHg using vasopressors in the NCCU. The CPP target will be based on the autoregulatory parameters of the individual patient utilising ICM+ software. The pressure reactivity index (PRx), is a measure of the ability of the cerebral vasculature to autoregulate to differing CPP (Czosnyka et al., 1997). Keeping the patient's CPP in this autoregulatory range has been show in observational studies to improve outcome (Aries et al., 2012, Needham et al., 2016). If the PRx is \>0.3, we will increase the CPP by 10-20 mmHg (to a maximum of 80mmHg as per the upper threshold suggested in the BTF guidelines) (Bratton et al., 2007a).
2. Diffusion Barrier Even with adequate oxygen delivery, microcirculatory collapse at the capillary level can lead to tissue hypoxia (Menon et al., 2004). In this circumstance, increasing the partial pressure of oxygen in arterial blood (PaO2) can increase the gradient between oxygen within the blood and the brain tissue and drive oxygen into the tissues (Reinert et al., 2003). This will be achieved by increasing the fractional inspired oxygen (FiO2) by 40% to a maximum FiO2 of 80%.
STAGE 3: Ensure adequate metabolic substrate delivery; increase brain glucose \>1.0 mmol/L Glucose is the primary biochemical substrate in order to generate pyruvate through glycolysis. Brain tissue hypoglycaemia, measured using microdialysis, has been shown to be common following TBI, and is correlated with an unfavourable outcome (Stein et al., 2012). If brain tissue glucose levels falls \<1.0 mmol/L, we will increase plasma glucose to 7-10 mmol/L, as lower levels have been shown to correlate to brain tissue hypoglacemia (Oddo et al., 2008), using 50% dextrose. Glucose manipulation has previously been demonstrated to improve LPR (Oddo et al., 2008).
STAGE 4: Persistent LPR\>25 despite all monitoring modalities normalized; consider mitochondrial dysfunction The mitochondria are the site of oxidative phosphorylation within cells generating Adenine-Tri-Phosphate (ATP) in the presence of oxygen and suitable biochemical substrate (typically pyruvate) in the tricarboxylic acid (TCA) cycle. It has been empirically demonstrated that following TBI, even in the presence of adequate oxygenation and glucose the mitochondria are incapable of utilising these substrates for energy generation(Verweij et al., 2000). In this circumstance, limited amounts of ATP are generated through anaerobic pathways generating lactate as a byproduct, thus increasing the LPR. In this case, LP ratio is increased, but with an a normal pyruvate concentration (\>70mmol/l). In this circumstance there are no accepted pharmacological therapies although in the literature both succinate, a component of the tricarboxcylic acid cycle (Ehinger et al., 2016), and Cyclosporin A, a calcineurin inhibitor, (Mbye et al., 2009) have shown potential efficacy against mitochondrial dysfunction, and Cyclosporin A has a proven safety profile in TBI patients (Mazzeo et al., 2009). It will be up to the treating physician to decide if they wish to consider novel neuroprotective agents or metabolic substrates that have shown promising results in the treatment of mitochondrial dysfunction.
Sampling strategies and data collection
Multimodality monitoring parameters are collected in the neuro-critical care unit (NCCU) in real time, including ICP, CPP (PRx) and PbO2 as well as potential treatments provided. Microdialysis parameters, including the brain metabolites glucose, pyruvate, lactate, glycerol and glutamate, will be sampled every 30 minutes by research nurses in the NCCU. When intracranial monitoring is not deemed necessary anymore, it will be discontinued as per conventional management. The number of interventions that the patient receives and any deviation from the protocol will be recorded.
Traumatic brain injury (TBI, "head injury) is a major cause of morbidity and mortality worldwide (Hyder et al., 2007). During the first four decades of life, trauma is the leading cause of death and TBI is involved in at least half the number of cases (Jennett, 1996). In the UK, 1,500 per 100,000 of the population (total 1 million) attend Accident and Emergency Departments with a head injury per year. Of these, around 135,000 people are admitted each year and there are an estimated 500,000 people (aged 16 - 74) with long term disabilities as a direct result of TBI (Headway, 2016). Approximately 10 per 100,000 per year die from head injury (Jennett and MacMillan, 1981, Hutchinson et al., 1998).
The major determinant of outcome from TBI is the severity of the primary injury, which is irreversible. However, primary injury invariably leads to the activation of cellular and molecular cascades which mediate further secondary injury that evolve over the ensuing hours and days (Masel and DeWitt, 2010) and are therefore amenable to therapeutic intervention. These molecular cascades can lead to brain swelling within the confines of a fixed intracranial compartment, leading to increased intracranial pressure (ICP) and compromising cerebral perfusion pressure (CPP) (Werner and Engelhard, 2007). The control of ICP and maintenance of CPP has been the bedrock of neurointensive care management of TBI for several decades, however, a recent multicenter randomised clinical trial could not show a long-term favorable outcome with ICP guided therapy (Carney et al., 2012).
The Neuro Critical Care Unit (NCCU) in Cambridge is a world leader in TBI monitoring and routinely employs multi-modal monitoring comprising of ICP, brain tissue oxygen and microdialysis monitoring, in every TBI patient. Conceptually, microdialysis monitoring is an attractive method of assessing tissue biochemistry as it provides a direct measure of metabolic substrates at the cellular level at which energy failure occurs. Specifically, the microdialysis derived measure Lactate/Pyruvate Ratio (LPR) is a measure of cellular redox state and therefore the balance between aerobic and anaerobic metabolism. To date, studies in the literature have focused on demonstrating that individual monitoring parameters e.g. microdialysis derived LPR\>25 correlate with an unfavorable outcome in multivariate analyses (Sarrafzadeh et al., 2000, Timofeev et al., 2011).
One reason that an ICP monitoring trial has not been proven to deliver improved outcome is that there are several alternative routes to neuronal injury include insufficient oxygen delivery (Nortje and Gupta, 2006), diffusion barrier within tissues (Smielewski et al., 2002), tissue hypoglycaemia (Vespa et al., 2003) and mitochondrial dysfunction (Verweij et al., 2000). Our understanding of these pathophysiological mechanisms has been greatly advanced by the use of multi-modality monitoring including direct measurement of brain tissue oxygen and cerebral microdialysis. In theory, these pathophysiological states could be treated using treatment of ICP lowering therapy, augmenting cerebral perfusion pressure (CPP), increasing oxygen delivery and augmenting glucose delivery. Though, we currently don't know the best way to combine these treatments and they are often used together making independent analysis difficult. Moreover, there is currently no approved therapy for mitochondrial dysfunction, and while some claim that mitochondrial dysfunction is imminent in increased LPR (Nordstrom et al., 2016), the reality is more complex as there will be conditions that are treatable with an increased LPR, but these states need to be better established for clinicians in order to accurately guide treatment (Lazaridis and Robertson, 2016). Previous implementations of guidelines in TBI have shown to improve care and reduce health related cost, something we hope to achieve with our established clinical protocol (Faul et al., 2007).
Overall research design
We propose a treatment algorithm exploring how a standardised clinical protocol that incorporates multi-modality monitoring parameters (intracranial pressure, brain tissue oxygen and microdialysis parameters) can be systematically and rigorously applied in a traumatic brain injury (TBI) patient cohort with deranged brain chemistry (LPR \>25).
Our principal outcome metric is the ability for the protocol to improve the LPR, as well as to see how many patients that may be stratified into any of the suggest treatment categories (see below).
Interventions and assessments
Following inclusion, patients will be monitored using the standard clinical monitoring for sedated and ventilated TBI patients which includes an Intracranial Pressure (ICP) monitor device, a brain tissue oxygen monitor (PbO2) and microdialysis to assess brain biochemistry (Le Roux et al., 2014, Hutchinson et al., 2015). While ICP and PbO2 are measured continually, microdialysis samples are measured hourly. If a derangement in LPR is identified (LPR\>25), patients will have an increase in monitoring frequency to every 30 minutes. Our primary measure of deranged energy generation at the cellular level is a LPR\>25. This threshold has been shown to relate to an unfavourable long-term outcome (Timofeev et al., 2011, Stein et al., 2012). If the LPR\>25 on two consecutive samples (to avoid spurious or transient derangements) it will trigger specific treatment strategies depending on the other contemporaneous monitoring modalities. After each intervention, two consecutive microdialysis samples will be taken to confirm whether LPR has been corrected or whether a further step in the protocol needs to be taken. The sequence of interventions has been chosen on the basis of the strength of association of each intervention with LPR in the existing literature (Hutchinson et al., 2015).
STAGE 1: Correction of Intracranial Hypertension; ICP corrected to \<20mmHg Raised ICP compromises delivery of both substrate and oxygen to the injured brain, by reducing Cerebral Perfusion Pressure) and is in itself an independent predictor of poor outcome (Marmarou et al., 1991, Bratton et al., 2007b). In the acute setting we will use hypertonic saline (100ml 5% saline by central venous bolus) as a rapid means of reducing ICP (Marko, 2012). This will be followed by an escalation of ICP control measures using our established ICP protocol (Helmy et al., 2007).
STAGE 2: Ensure sufficient Oxygenation; increase PbO2\>15mmHg
Increased LPR can reflect ischaemia and in the first instance we will ensure that there is adequate oxygenation by increasing the PbO2\>15mmHg. This threshold of PbO2 has been recognised as physiological in the literature (van den Brink et al., 2000). There are two possible limitations to oxygen availability to brain tissue recognised in TBI:
1. Inadequate oxygen delivery (DO2(brain)=Cerebral Blood Flow (CBF) x Oxygen Capacity in Blood) Firstly, we will ensure adequate haemoglobin concentration (\>8g/dl) within the blood and normovolemia to ensure adequate oxygen carrying capacity. Cerebral perfusion pressure (CPP) is monitored as a surrogate of CBF and is usually maintained at around 60-80 mmHg using vasopressors in the NCCU. The CPP target will be based on the autoregulatory parameters of the individual patient utilising ICM+ software. The pressure reactivity index (PRx), is a measure of the ability of the cerebral vasculature to autoregulate to differing CPP (Czosnyka et al., 1997). Keeping the patient's CPP in this autoregulatory range has been show in observational studies to improve outcome (Aries et al., 2012, Needham et al., 2016). If the PRx is \>0.3, we will increase the CPP by 10-20 mmHg (to a maximum of 80mmHg as per the upper threshold suggested in the BTF guidelines) (Bratton et al., 2007a).
2. Diffusion Barrier Even with adequate oxygen delivery, microcirculatory collapse at the capillary level can lead to tissue hypoxia (Menon et al., 2004). In this circumstance, increasing the partial pressure of oxygen in arterial blood (PaO2) can increase the gradient between oxygen within the blood and the brain tissue and drive oxygen into the tissues (Reinert et al., 2003). This will be achieved by increasing the fractional inspired oxygen (FiO2) by 40% to a maximum FiO2 of 80%.
STAGE 3: Ensure adequate metabolic substrate delivery; increase brain glucose \>1.0 mmol/L Glucose is the primary biochemical substrate in order to generate pyruvate through glycolysis. Brain tissue hypoglycaemia, measured using microdialysis, has been shown to be common following TBI, and is correlated with an unfavourable outcome (Stein et al., 2012). If brain tissue glucose levels falls \<1.0 mmol/L, we will increase plasma glucose to 7-10 mmol/L, as lower levels have been shown to correlate to brain tissue hypoglacemia (Oddo et al., 2008), using 50% dextrose. Glucose manipulation has previously been demonstrated to improve LPR (Oddo et al., 2008).
STAGE 4: Persistent LPR\>25 despite all monitoring modalities normalized; consider mitochondrial dysfunction The mitochondria are the site of oxidative phosphorylation within cells generating Adenine-Tri-Phosphate (ATP) in the presence of oxygen and suitable biochemical substrate (typically pyruvate) in the tricarboxylic acid (TCA) cycle. It has been empirically demonstrated that following TBI, even in the presence of adequate oxygenation and glucose the mitochondria are incapable of utilising these substrates for energy generation(Verweij et al., 2000). In this circumstance, limited amounts of ATP are generated through anaerobic pathways generating lactate as a byproduct, thus increasing the LPR. In this case, LP ratio is increased, but with an a normal pyruvate concentration (\>70mmol/l). In this circumstance there are no accepted pharmacological therapies although in the literature both succinate, a component of the tricarboxcylic acid cycle (Ehinger et al., 2016), and Cyclosporin A, a calcineurin inhibitor, (Mbye et al., 2009) have shown potential efficacy against mitochondrial dysfunction, and Cyclosporin A has a proven safety profile in TBI patients (Mazzeo et al., 2009). It will be up to the treating physician to decide if they wish to consider novel neuroprotective agents or metabolic substrates that have shown promising results in the treatment of mitochondrial dysfunction.
Sampling strategies and data collection
Multimodality monitoring parameters are collected in the neuro-critical care unit (NCCU) in real time, including ICP, CPP (PRx) and PbO2 as well as potential treatments provided. Microdialysis parameters, including the brain metabolites glucose, pyruvate, lactate, glycerol and glutamate, will be sampled every 30 minutes by research nurses in the NCCU. When intracranial monitoring is not deemed necessary anymore, it will be discontinued as per conventional management. The number of interventions that the patient receives and any deviation from the protocol will be recorded.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Traumatic Brain INjury
Microdialysis
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Observational Model Type
COHORT
Study Time Perspective
PROSPECTIVE
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients with head injury requiring ICP monitoring
* Age 18-65 years
* Abnormal CT scan
* Age 18-65 years
* Abnormal CT scan
Exclusion Criteria
* Bilateral fixed and dilated pupils
* Bleeding diathesis
* Thrombocytopenia (platelets \< 100)
* Devastating injuries; patient not expected to survive \> 24 hours
* Brainstem damage
* Pregnancy
* Involvement in other studies non-observational studies
* MD catheter located in haemorrhagic lesion
* Bleeding diathesis
* Thrombocytopenia (platelets \< 100)
* Devastating injuries; patient not expected to survive \> 24 hours
* Brainstem damage
* Pregnancy
* Involvement in other studies non-observational studies
* MD catheter located in haemorrhagic lesion
Minimum Eligible Age
18 Years
Maximum Eligible Age
65 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Cambridge University Hospitals NHS Foundation Trust
OTHER
Sponsor Role
collaborator
University of Cambridge
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Adel Helmy
University Lecturer Neurosurgery
Responsibility Role
PRINCIPAL_INVESTIGATOR
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Cambridge University Hospital NHS Trust
Cambridge, Cambridgeshire, United Kingdom
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United Kingdom
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Adel Helmy
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341-53.
Reference Type
BACKGROUND
Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry. 1996 Apr;60(4):362-9. doi: 10.1136/jnnp.60.4.362. No abstract available.
Reference Type
BACKGROUND
Jennett B, MacMillan R. Epidemiology of head injury. Br Med J (Clin Res Ed). 1981 Jan 10;282(6258):101-4. doi: 10.1136/bmj.282.6258.101.
Reference Type
BACKGROUND
Hutchinson PJ, Kirkpatrick PJ, Addison J, Jackson S, Pickard JD. The management of minor traumatic brain injury. J Accid Emerg Med. 1998 Mar;15(2):84-8. doi: 10.1136/emj.15.2.84.
Reference Type
BACKGROUND
Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma. 2010 Aug;27(8):1529-40. doi: 10.1089/neu.2010.1358.
Reference Type
BACKGROUND
Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007 Jul;99(1):4-9. doi: 10.1093/bja/aem131.
Reference Type
BACKGROUND
Carney N, Lujan S, Dikmen S, Temkin N, Petroni G, Pridgeon J, Barber J, Machamer J, Cherner M, Chaddock K, Hendrix T, Rondina C, Videtta W, Celix JM, Chesnut R. Intracranial pressure monitoring in severe traumatic brain injury in latin america: process and methods for a multi-center randomized controlled trial. J Neurotrauma. 2012 Jul 20;29(11):2022-9. doi: 10.1089/neu.2011.2019. Epub 2012 May 15.
Reference Type
BACKGROUND
Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O'Connell MT, Czosnyka M, Smielewski P, Pickard JD, Menon DK, Kirkpatrick PJ, Gupta AK, Hutchinson PJ. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain. 2011 Feb;134(Pt 2):484-94. doi: 10.1093/brain/awq353. Epub 2011 Jan 18.
Reference Type
BACKGROUND
Sarrafzadeh AS, Sakowitz OW, Callsen TA, Lanksch WR, Unterberg AW. Bedside microdialysis for early detection of cerebral hypoxia in traumatic brain injury. Neurosurg Focus. 2000 Nov 15;9(5):e2. doi: 10.3171/foc.2000.9.5.2.
Reference Type
BACKGROUND
Nortje J, Gupta AK. The role of tissue oxygen monitoring in patients with acute brain injury. Br J Anaesth. 2006 Jul;97(1):95-106. doi: 10.1093/bja/ael137. Epub 2006 Jun 3.
Reference Type
BACKGROUND
Smielewski P, Coles JP, Fryer TD, Minhas PS, Menon DK, Pickard JD. Integrated image analysis solutions for PET datasets in damaged brain. J Clin Monit Comput. 2002 Dec;17(7-8):427-40. doi: 10.1023/a:1026293611455.
Reference Type
BACKGROUND
Vespa PM, McArthur D, O'Phelan K, Glenn T, Etchepare M, Kelly D, Bergsneider M, Martin NA, Hovda DA. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab. 2003 Jul;23(7):865-77. doi: 10.1097/01.WCB.0000076701.45782.EF.
Reference Type
BACKGROUND
Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP. Impaired cerebral mitochondrial function after traumatic brain injury in humans. J Neurosurg. 2000 Nov;93(5):815-20. doi: 10.3171/jns.2000.93.5.0815.
Reference Type
BACKGROUND
Nordstrom CH, Nielsen TH, Schalen W, Reinstrup P, Ungerstedt U. Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion. Acta Neurochir (Wien). 2016 Jul;158(7):1231-40. doi: 10.1007/s00701-016-2835-z. Epub 2016 May 17.
Reference Type
BACKGROUND
Lazaridis C, Robertson CS. The Role of Multimodal Invasive Monitoring in Acute Traumatic Brain Injury. Neurosurg Clin N Am. 2016 Oct;27(4):509-17. doi: 10.1016/j.nec.2016.05.010.
Reference Type
BACKGROUND
Faul M, Wald MM, Rutland-Brown W, Sullivent EE, Sattin RW. Using a cost-benefit analysis to estimate outcomes of a clinical treatment guideline: testing theBrain Trauma Foundation guidelines for the treatment of severe traumatic brain injury. J Trauma. 2007 Dec;63(6):1271-8. doi: 10.1097/TA.0b013e3181493080.
Reference Type
BACKGROUND
Hutchinson PJ, Jalloh I, Helmy A, Carpenter KL, Rostami E, Bellander BM, Boutelle MG, Chen JW, Claassen J, Dahyot-Fizelier C, Enblad P, Gallagher CN, Helbok R, Hillered L, Le Roux PD, Magnoni S, Mangat HS, Menon DK, Nordstrom CH, O'Phelan KH, Oddo M, Perez Barcena J, Robertson C, Ronne-Engstrom E, Sahuquillo J, Smith M, Stocchetti N, Belli A, Carpenter TA, Coles JP, Czosnyka M, Dizdar N, Goodman JC, Gupta AK, Nielsen TH, Marklund N, Montcriol A, O'Connell MT, Poca MA, Sarrafzadeh A, Shannon RJ, Skjoth-Rasmussen J, Smielewski P, Stover JF, Timofeev I, Vespa P, Zavala E, Ungerstedt U. Consensus statement from the 2014 International Microdialysis Forum. Intensive Care Med. 2015 Sep;41(9):1517-28. doi: 10.1007/s00134-015-3930-y.
Reference Type
BACKGROUND
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Related Links
Access external resources that provide additional context or updates about the study.
https://www.headway.org.uk/about-brain-injury/further-information/statistics/
Head injury statistics in the UK
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
A094233
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Acute and Mild TBI Injury in Military and Civilian Population Using Advanced MR Imaging
NCT05101239
ACTIVE_NOT_RECRUITING
Mild Traumatic Brain Injury Discrimination
NCT02453958
COMPLETED
NA
Effect of Multimodal Monitoring Cluster Management on Patients with Severe Traumatic Brain Injury
NCT06583252
RECRUITING
Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study)
NCT04318665
COMPLETED
NA
CENTER-TBI: Collaborative European NeuroTrauma Effectiveness Research in TBI
NCT02210221
COMPLETED
Computed Tomography Perfusion in Patients With Severe Head Injury
NCT02756585
COMPLETED
NA
Imaging of Injury Mechanism and Interaction of Intestinal Bacteria in Children With Mild Traumatic Brain Injury
NCT05090007
UNKNOWN
Objective Concussion Assessment Using MRI and Metabolomics
NCT05993351
RECRUITING
Multimodal Neuroimaging Analysis After Mild Traumatic Brain Injury
NCT03342612
TERMINATED
NA
Transcranial Doppler on Admission of Patients With Mild to Moderate Traumatic Brain Injury
NCT01291706
COMPLETED
TBI-Prognosis Multicenter Prospective Study
NCT02452541
UNKNOWN
NA
Contributions of mTBI to Neurodegeneration Due to Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease (AD)
NCT04124029
RECRUITING
Multimodal Brain Monitoring as an Early Warning and Prognostic Tool for Acute Brain Injury
NCT06505213
NOT_YET_RECRUITING
Developing and Validating Blood and Imaging BIOmarkers of AXonal Injury Following Traumatic Brain Injury
NCT03534154
COMPLETED
The Value of Multimodal MR Imaging in Cognitive Assessment of Patients With Moderate Traumatic Brain Injury
NCT06099210
RECRUITING
Evaluating a Novel Method of EEG Evoked Response Potential Analysis in Concussion Assessment
NCT03265912
COMPLETED
Imaging Biomarkers of Mild Traumatic Brain Injury: a Longitudinal Cohort Study
NCT02868684
COMPLETED
Transforming Research and Clinical Knowledge in Traumatic Brain Injury
NCT02119182
COMPLETED
Advanced MRI In Acute Military TBI
NCT01313130
UNKNOWN
Cerebral Desaturation in Traumatic Brain Injury
NCT02810145
UNKNOWN
Transcranial Doppler in Mild and Moderate Traumatic Brain Injury (TBI)
NCT05151978
UNKNOWN
Mild Traumatic Brain Injury Registry
NCT01688869
COMPLETED
Advanced MRI Applications for Mild Traumatic Brain Injury-Phase 2
NCT02556177
COMPLETED
NA
Olfactory Function in Patients With Acute Mild Traumatic Brain Injury
NCT02977728
COMPLETED