Traumatic Brain INjuryPhase 2IL1raNCT02997371
IL-1ra Dose-range Study for Moderate-to-severe TBI Patients
A Phase 2 study testing Anakinra Prefilled Syringe and Isotonic saline in people with Traumatic Brain INjury, run by Adel Helmy at 1 site in United Kingdom.
Trial summary
Traumatic brain injury (TBI) is a common condition with high degree of morbidity and mortality (Hyder et al., 2007). Current treatment paradigms for TBI focus on mitigating secondary injury and maintaining cerebral physiology (Carney et al., 2016), however, there are currently no approved drugs that target the… 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?
- Anakinra Prefilled Syringe and Isotonic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2017to Oct 2021
- Phase
- Phase 2
- 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
- Suffer from a TBI, present with a Glasgow Coma Scale (GCS) of 3-13 and be deemed to be in need of neuro-critical care and intracranial monitoring for at least 72 hours.
- Be aged 18-65
- The first dose of Kineret (or placebo) must be provided within 12 hours after trauma.
Who cannot join
- Head injury unlikely to survive 5 days (radiological evidence of above as judged by clinical team, bilateral fixed and dilated pupils).
- Follow up not possible
- Not suitable for insertion of cranial access device to monitor the brain (such as bleeding complications)
- Active immunosuppression therapy (evidence of neutropenia, immunosuppression secondary to immunomodulatory medications, chemotherapy or radiation therapy in the 3 months preceding study entry)
- Severe Renal Insufficiency or End Stage Renal Disease (defined as a creatinine clearance <30 ml/min)
- Pregnancy/Nursing mothers
- Known hypersensitivity to E. coli derived products
- Administration of live vaccine
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cambridge University Hospital NHS Trust
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A Randomised Double Blind Placebo Controlled Dose-range Study Using Placebo, 1.5g and 3.0g of Intravenous Recombinant Interleukin-1 Receptor Antagonist (Anakinra) for Patients With Moderate-to-severe TBI
Traumatic brain injury (TBI) is a common condition with high degree of morbidity and mortality (Hyder et al., 2007). Current treatment paradigms for TBI focus on mitigating secondary injury and maintaining cerebral physiology (Carney et al., 2016), however, there are currently no approved drugs that target the underlying conditions for patients suffering from TBI (Bullock et al., 1999). It is increasingly recognised that the innate inflammatory response to TBI may inflict injury (Lucas et al., 2006), and one of the most prominent mediators of inflammation in the injured brain is the Interleukin-1 (IL-1) receptor pathway (Allan et al., 2005). An endogenous antagonist to IL-1, is available in recombinant form (IL-1ra, Kineret), and is known to be safe in TBI (Helmy et al., 2014).
In order to fully understand, and potentially optimize, the effect of Kineret, the investigators wish to conduct a dose-response study by giving three cohorts (n=20 per group) either placebo (isotonic saline), 1.5g or 3.0g of active substance administered intravenously in a double-blind, randomized setting. The concentrations have in previous studies not been shown to present any side-effects (Singh et al., 2014). The drug will be provided within 12 hours after trauma. The goal will be to provide a dose-response effect on the cerebral inflammatory response. As secondary goals, the investigators will assess the brain damage by measuring proteins in blood and cerebrospinal fluid, functional outcome and inflammation in the brain using positron emission tomography.
Read the detailed description
Aim
The hypothesis is that an increasing dose of the anti-inflammatory drug recombinant human Interleukin-1 receptor antagonist (IL-1ra, Kineret) will modulate the inflammatory state of the traumatically injured brain, which will attenuate the injurious processes that occur following TBI.
Study Design
While different doses of Anakinra have been used in trials, there is no knowledge of what constitutes an optimized concentration of the drug. To address this limitation, the current study will be a dose-response study in a double blind randomised clinical fashion, using placebo (n=20), 1.5 g ("intermediate dose") or (n=20) and 3.0 g ("high dose")(n=20) of Anakinra provided the first 48 hours (drug/placebo administered initially as 500 mg infusion bolus and later as an 1g or 2.5g infusion for 48 hours). Thus, a total of n=60 patients will be included. Sample-size analyses have indicated that the number of patients is sufficient to detect differences in the inflammatory response as gauged with cytokine measurements using cerebral microdialysis.
As surrogate markers of outcome for these patients, several protein biomarkers of brain injury and proteins of the innate immune responses will be quantified using techniques called ELISA and multiplex assay technology. The investigators also wish to use radiological techniques, such as magnetic resonance imaging to study damages in white matter tracts in the brain and positron emission tomography to assess the degree of microglial activation. All these methods will be used to assess the potential benefit of the treatment vs placebo.
By this type of study design, it will minimize bias and confounders that may influence the study.
Patient Recruitment
Patients with a clinical diagnosis of severe and moderate TBI will be identified by the research team at the daily departmental neuro-critical care unit meeting. Patients meeting the inclusion criteria will be approached for consent/assent if conscious or if next of kin is present. If not, consent will be assumed as we know Anakinra to be safe and there is likely to be a narrow therapeutic window. With the current patient load at Addenbrooke's Hospital, Cambridge, the investigators deem it possible to recruit one patient per week, thus estimating that the recruiting phase will take approximately two years to complete.
Sampling
All the sampling will be conducted during the acute phase when the patient is unconscious in the neuro-critical care unit. Microdialysis probes are sampled hourly. To assess inflammatory activity in the brain, positron emission tomography will be performed within the first week and after 2-3 weeks. Magnetic resonance imaging will be performed the first 2-3 weeks and then after 6 months. To measure the patient's adaptive immune response to brain specific proteins, specialised auto-immunisation assays will be performed on patient blood at day 1-3 following injury as well as after 2-3 weeks.
During the intensive care phase, blood and cerebrospinal fluid will be sampled twice per day (approximately 3mL per sampling time per compartment, volumes that we do not deem harmful to the patient) and will be collected together with hourly microdialysate fluid samples the first 7 days from admission. Blood will also be sampled at an outpatient clinic follow up at 6 and 12 months following injury. Patient samples will be anonymised and stored at -80degC in the Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge before analysis.
It will not to be possible to measure cytokines, the drug and biomarkers from all microdialysis samples due to volume constraints. Moreover, we believe that a temporal resolution of 6 hours is probably adequate for the brain concentration of the drug while 12 hours is sufficient in serum. APP and tau will also be measured every 6 hours. The only parameter that will be hourly analysed in microdialysis is cytokine and chemokines through a luminex panel.
Clinical Follow-up
Patients will be followed up at a clinic visit at 6 and 12 months after trauma by questionnaire survey using standardised outcome measures in neurosurgical patients including the golden standard extended Glasgow Outcome Score and Short Form 36.
- Conditions
- Traumatic Brain INjury
- Being tested
- Anakinra Prefilled Syringe, Isotonic saline
- Keywords
- Traumatic brain injury, Microdialysis, Interleukin-1 receptor antagonist, Magnetic Resonance Imaging, Positron Emission Tomography
- 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.
Anakinra Prefilled SyringeDrug
Also called Kineret
Administration as initially intravenous injection followed by a intravenous infusion
Isotonic salineDrug
Also called Placebo
Placebo, administration as initially intravenous injection followed by a intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Isotonic saline administered as an injection and infusion Receives: Drug: Isotonic saline |
| 1.5 g Kineret | Experimental | Kineret provided as a 500 mg injection followed by a 1g infusion. Receives: Drug: Anakinra Prefilled Syringe |
| 3.0 g Kineret | Experimental | Kineret provided as a 500 mg injection followed by a 2.5g infusion. Receives: Drug: Anakinra Prefilled Syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease of pro-inflammatory cytokines in brain extracellular fluid (ECF)
Decrease of Tumor necrosis factor alpha and interferon gamma cytokines in brain ECF
Measured: First 48 hours
Secondary outcomes (17)
Patient outcome GOSe
Extended Glasgow Outcome Score (GOSe) assessments at 6 months and 1 year.
Measured: 6 months and 12 months
Patient outcome SF36
Short Form - 36 (SF-36) assessments at 6 months and 1 year.
Measured: 6 months and 12 months
Imaging outcome - PET-MRI
To determine degree of microglial activation globally and in the locality of the microdialysis catheter, using magnetic resonance imaging (MRI) in combination with positron emission tomography (PET) PK-11195 (an an isoquinoline carboxamide) ligand.
Measured: During the first 14 days
Imaging outcome - DTI-MRI
To determine degree of axonal injury globally and in the locality of the microdialysis catheter, using magnetic resonance imaging (MRI) in combination with diffuse tensor imaging (DTI).
Measured: During the first 14 days
Biochemical outcome - S100B
Concentrations of protein biomarkers of tissue fate, S100B in serum (µg/L) twice per day as well as after 6 months and 12 months.
Measured: During the first 7 days + at 6 months and 12 months
Biochemical outcome - NF-L
Concentrations of protein biomarkers of tissue fate, Concentrations of protein biomarkers of tissue fate, Neurofilament Light (NF-L) in serum (µg/L) twice per day as well as after 6 months and 12 months.
Measured: During the first 7 days
Biochemical outcome - Tau
Concentrations of protein biomarkers of tissue fate, microtubuli associated protein tau (tau) measured in microdialysis every 6 hours.
Measured: During the first 7 days
Biochemical outcome - APP
Concentrations of protein biomarkers of tissue fate, Amyloid Precursor Protein Beta (APP) associated protein tau measured in microdialysis every 6 hours.
Measured: During the first 7 days
Biochemical outcome - Autoreactivity versus MBP
Concentration of circulating T-cells with autoreactivity towards myelin basic protein (MBP) in serum.
Measured: During the first 7 days + at 6 months and 12 months
Monitoring outcome - ICP
Intracranial pressure (ICP, mmHg) during the neuro-critical care unit (NCCU) stay.
Measured: First 7 days
Monitoring outcome - CPP
Cerebral perfusion pressure (CPP, mmHg) during the NCCU stay.
Measured: First 7 days
Monitoring outcome - Cerebral Metabolism LPR
Cerebral metabolism, by measuring lactate:pyruvate ratio (LPR) in microdialysis.
Measured: First 7 days
Monitoring outcome - Brain tissue oxygenation
Brain tissue oxygen (mmHg).
Measured: First 7 days
Monitoring outcome - PRx
Derived variables of cerebral elastance (Pressure reactivity index, PRx).
Measured: First 7 days
Pharmacological outcome - Concentration of IL1ra in brain tissue
IL-1ra brain concentration (pg/ml), measured every 6 hours by cerebral microdialysis.
Measured: First week
Pharmacological outcome - Concentration of IL1ra in serum
IL-1ra serum concentration (pg/ml), measured every 12 hours.
Measured: First week
Side effects of the IL1ra
To study any potential side-effect of the drug, both known and unknown.
Measured: First week + up to 12 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study startOct 2017 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionOct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adel Helmy
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Adel Helmy, University of Cambridge
- Investigators
- Adel Helmy, MA, MB BChir, FRCS, PhD, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997371
- Sponsor's protocol ID
- CCTU0185
- Acronym
- IL1ra
- Status last verified
- May 2017
- First submitted
- 7 Dec 2016
- Last updated
- 8 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol. 2005 Aug;5(8):629-40. doi: 10.1038/nri1664.
PubMed 16034365Bullock MR, Lyeth BG, Muizelaar JP. Current status of neuroprotection trials for traumatic brain injury: lessons from animal models and clinical studies. Neurosurgery. 1999 Aug;45(2):207-17; discussion 217-20. doi: 10.1097/00006123-199908000-00001.
PubMed 10449064Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432.
PubMed 27654000Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, Hutchinson PJ. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial. J Cereb Blood Flow Metab. 2014 May;34(5):845-51. doi: 10.1038/jcbfm.2014.23. Epub 2014 Feb 26.
PubMed 24569690Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341-53.
PubMed 18162698Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S232-40. doi: 10.1038/sj.bjp.0706400.
PubMed 16402109Singh N, Hopkins SJ, Hulme S, Galea JP, Hoadley M, Vail A, Hutchinson PJ, Grainger S, Rothwell NJ, King AT, Tyrrell PJ. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflammation. 2014 Jan 3;11:1. doi: 10.1186/1742-2094-11-1.
PubMed 24383930
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Double Blind Placebo Controlled Dose-range Study Using Placebo, 1.5g and 3.0g of Intravenous Recombinant Interleukin-1 Receptor Antagonist (Anakinra) for Patients With Moderate-to-severe TBI
- ClinicalTrials.gov ID
- NCT02997371
- Acronym / sponsor ID
- IL1ra / CCTU0185
- Conditions
- Traumatic Brain INjury
- Keywords
- Traumatic brain injury, Microdialysis, Interleukin-1 receptor antagonist, Magnetic Resonance Imaging, Positron Emission Tomography
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Adel HelmyUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Study start
- Oct 2017 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2021 (estimated)
- First posted
- 20 Dec 2016 (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 injury (TBI) is a common condition with high degree of morbidity and mortality (Hyder et al., 2007). Current treatment paradigms for TBI focus on mitigating secondary injury and maintaining cerebral physiology (Carney et al., 2016), however, there are currently no approved drugs that target the underlying conditions for patients suffering from TBI (Bullock et al., 1999). It is increasingly recognised that the innate inflammatory response to TBI may inflict injury (Lucas et al., 2006), and one of the most prominent mediators of inflammation in the injured brain is the Interleukin-1 (IL-1) receptor pathway (Allan et al., 2005). An endogenous antagonist to IL-1, is available in recombinant form (IL-1ra, Kineret), and is known to be safe in TBI (Helmy et al., 2014).
In order to fully understand, and potentially optimize, the effect of Kineret, the investigators wish to conduct a dose-response study by giving three cohorts (n=20 per group) either placebo (isotonic saline), 1.5g or 3.0g of active substance administered intravenously in a double-blind, randomized setting. The concentrations have in previous studies not been shown to present any side-effects (Singh et al., 2014). The drug will be provided within 12 hours after trauma. The goal will be to provide a dose-response effect on the cerebral inflammatory response. As secondary goals, the investigators will assess the brain damage by measuring proteins in blood and cerebrospinal fluid, functional outcome and inflammation in the brain using positron emission tomography.
Detailed description
Aim
The hypothesis is that an increasing dose of the anti-inflammatory drug recombinant human Interleukin-1 receptor antagonist (IL-1ra, Kineret) will modulate the inflammatory state of the traumatically injured brain, which will attenuate the injurious processes that occur following TBI.
Study Design
While different doses of Anakinra have been used in trials, there is no knowledge of what constitutes an optimized concentration of the drug. To address this limitation, the current study will be a dose-response study in a double blind randomised clinical fashion, using placebo (n=20), 1.5 g ("intermediate dose") or (n=20) and 3.0 g ("high dose")(n=20) of Anakinra provided the first 48 hours (drug/placebo administered initially as 500 mg infusion bolus and later as an 1g or 2.5g infusion for 48 hours). Thus, a total of n=60 patients will be included. Sample-size analyses have indicated that the number of patients is sufficient to detect differences in the inflammatory response as gauged with cytokine measurements using cerebral microdialysis.
As surrogate markers of outcome for these patients, several protein biomarkers of brain injury and proteins of the innate immune responses will be quantified using techniques called ELISA and multiplex assay technology. The investigators also wish to use radiological techniques, such as magnetic resonance imaging to study damages in white matter tracts in the brain and positron emission tomography to assess the degree of microglial activation. All these methods will be used to assess the potential benefit of the treatment vs placebo.
By this type of study design, it will minimize bias and confounders that may influence the study.
Patient Recruitment
Patients with a clinical diagnosis of severe and moderate TBI will be identified by the research team at the daily departmental neuro-critical care unit meeting. Patients meeting the inclusion criteria will be approached for consent/assent if conscious or if next of kin is present. If not, consent will be assumed as we know Anakinra to be safe and there is likely to be a narrow therapeutic window. With the current patient load at Addenbrooke's Hospital, Cambridge, the investigators deem it possible to recruit one patient per week, thus estimating that the recruiting phase will take approximately two years to complete.
Sampling
All the sampling will be conducted during the acute phase when the patient is unconscious in the neuro-critical care unit. Microdialysis probes are sampled hourly. To assess inflammatory activity in the brain, positron emission tomography will be performed within the first week and after 2-3 weeks. Magnetic resonance imaging will be performed the first 2-3 weeks and then after 6 months. To measure the patient's adaptive immune response to brain specific proteins, specialised auto-immunisation assays will be performed on patient blood at day 1-3 following injury as well as after 2-3 weeks.
During the intensive care phase, blood and cerebrospinal fluid will be sampled twice per day (approximately 3mL per sampling time per compartment, volumes that we do not deem harmful to the patient) and will be collected together with hourly microdialysate fluid samples the first 7 days from admission. Blood will also be sampled at an outpatient clinic follow up at 6 and 12 months following injury. Patient samples will be anonymised and stored at -80degC in the Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge before analysis.
It will not to be possible to measure cytokines, the drug and biomarkers from all microdialysis samples due to volume constraints. Moreover, we believe that a temporal resolution of 6 hours is probably adequate for the brain concentration of the drug while 12 hours is sufficient in serum. APP and tau will also be measured every 6 hours. The only parameter that will be hourly analysed in microdialysis is cytokine and chemokines through a luminex panel.
Clinical Follow-up
Patients will be followed up at a clinic visit at 6 and 12 months after trauma by questionnaire survey using standardised outcome measures in neurosurgical patients including the golden standard extended Glasgow Outcome Score and Short Form 36.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Isotonic salineIsotonic saline administered as an injection and infusion |
| 1.5 g Kineret | Experimental | Drug: Anakinra Prefilled SyringeKineret provided as a 500 mg injection followed by a 1g infusion. |
| 3.0 g Kineret | Experimental | Drug: Anakinra Prefilled SyringeKineret provided as a 500 mg injection followed by a 2.5g infusion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Suffer from a TBI, present with a Glasgow Coma Scale (GCS) of 3-13 and be deemed to be in need of neuro-critical care and intracranial monitoring for at least 72 hours.
- Be aged 18-65
- The first dose of Kineret (or placebo) must be provided within 12 hours after trauma.
Key exclusion criteria (8 listed)
- Head injury unlikely to survive 5 days (radiological evidence of above as judged by clinical team, bilateral fixed and dilated pupils).
- Follow up not possible
- Not suitable for insertion of cranial access device to monitor the brain (such as bleeding complications)
- Active immunosuppression therapy (evidence of neutropenia, immunosuppression secondary to immunomodulatory medications, chemotherapy or radiation therapy in the 3 months preceding study entry)
- Severe Renal Insufficiency or End Stage Renal Disease (defined as a creatinine clearance <30 ml/min)
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 |
|---|---|---|
| Anakinra Prefilled SyringeAlso: KineretAdministration as initially intravenous injection followed by a intravenous infusion | Drug | 1.5 g Kineret, 3.0 g Kineret |
| Isotonic salineAlso: PlaceboPlacebo, administration as initially intravenous injection followed by a intravenous infusion | Drug | Placebo |
Primary outcome
Decrease of pro-inflammatory cytokines in brain extracellular fluid (ECF)
Time frame: First 48 hours
Decrease of Tumor necrosis factor alpha and interferon gamma cytokines in brain ECF
17 secondary outcomes
Patient outcome GOSe
Time frame: 6 months and 12 months
Patient outcome SF36
Time frame: 6 months and 12 months
Imaging outcome - PET-MRI
Time frame: During the first 14 days
Imaging outcome - DTI-MRI
Time frame: During the first 14 days
Biochemical outcome - S100B
Time frame: During the first 7 days + at 6 months and 12 months
Biochemical outcome - NF-L
Time frame: During the first 7 days
Biochemical outcome - Tau
Time frame: During the first 7 days
Biochemical outcome - APP
Time frame: During the first 7 days
Biochemical outcome - Autoreactivity versus MBP
Time frame: During the first 7 days + at 6 months and 12 months
Monitoring outcome - ICP
Time frame: First 7 days
Monitoring outcome - CPP
Time frame: First 7 days
Monitoring outcome - Cerebral Metabolism LPR
Time frame: First 7 days
Monitoring outcome - Brain tissue oxygenation
Time frame: First 7 days
Monitoring outcome - PRx
Time frame: First 7 days
Pharmacological outcome - Concentration of IL1ra in brain tissue
Time frame: First week
Pharmacological outcome - Concentration of IL1ra in serum
Time frame: First week
Side effects of the IL1ra
Time frame: First week + up to 12 months follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Background: PubMed 16034365Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol. 2005 Aug;5(8):629-40. doi: 10.1038/nri1664.
- Background: PubMed 10449064Bullock MR, Lyeth BG, Muizelaar JP. Current status of neuroprotection trials for traumatic brain injury: lessons from animal models and clinical studies. Neurosurgery. 1999 Aug;45(2):207-17; discussion 217-20. doi: 10.1097/00006123-199908000-00001.
- Background: PubMed 27654000Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432.
- Background: PubMed 24569690Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, Hutchinson PJ. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial. J Cereb Blood Flow Metab. 2014 May;34(5):845-51. doi: 10.1038/jcbfm.2014.23. Epub 2014 Feb 26.
- Background: PubMed 18162698Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341-53.
- Background: PubMed 16402109Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S232-40. doi: 10.1038/sj.bjp.0706400.
- Background: PubMed 24383930Singh N, Hopkins SJ, Hulme S, Galea JP, Hoadley M, Vail A, Hutchinson PJ, Grainger S, Rothwell NJ, King AT, Tyrrell PJ. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflammation. 2014 Jan 3;11:1. doi: 10.1186/1742-2094-11-1.
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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.
Adel Helmy, MA, MB BChir, FRCS, PhD principal investigator
University of Cambridge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra Prefilled Syringe and Isotonic saline in people with Traumatic Brain INjury, run by Adel Helmy at 1 site in United Kingdom.
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 8 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: status not confirmed, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adel Helmy, MA, MB BChir, FRCS, PhD (00441223 216147, adelhelmy@cantab.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease of pro-inflammatory cytokines in brain extracellular fluid (ECF) (time frame: First 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02997371, which also lists 7 linked publications.
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 8 May 2017.