Evidence map›Paper›PMID 24569690›Full record

Trial reportJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2014

Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.

Adel Helmy, Mathew R Guilfoyle, Keri L H Carpenter, John D Pickard, David K Menon, Peter J Hutchinson

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 109 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 4 pooled it
12.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02997371 phase2unknown statusnot on this mapstarted 2017, after this paper: background citation

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

TypeinterventionalSponsorAdel HelmyRan2017 to 2021Enrolled60ConditionsTraumatic Brain INjuryArmsAnakinra Prefilled Syringe, Isotonic saline
NCT04631471 phase3recruitingnot on this mapstarted 2021, after this paper: background citation

Regeneration in Cervical Degenerative Myelopathy - a Multi-centre, Double-blind, Randomised, Placebo Controlled Trial Assessing the Efficacy of Ibudilast as an Adjuvant Treatment to Decompressive Surgery for Degenerative Cervical Myelopathy

TypeinterventionalSponsorCambridge University Hospitals NHS Foundation TrustRan2021 to 2026Enrolled400ConditionsMyelopathy, Spinal Cord DiseasesArmsIbudilast, Cervical decompressive surgery, Matching placebo
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 4 syntheses or guidelines pooled it, 181 citations in OpenAlex.

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  13. CSF1R and IL1R1 inhibitors synergistically attenuate the early pathogenesis of traumatic brain injury in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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  15. Modulation of adult hippocampal neurogenesis by interleukin 1 signaling.Neurobiology of sleep and circadian rhythms · 2025
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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Adel HelmyDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Mathew R GuilfoyleDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Keri L H Carpenter1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
John D Pickard1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
David K Menon1] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
Peter J Hutchinson1] Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK [2] Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
University of Cambridge · GB

Funding

Department of Health NIHR-RP-R3-12-013Medical Research Council G0001354Medical Research Council G0600986Medical Research Council G0600986 ID 79068Medical Research Council G0802251Medical Research Council G1000183Medical Research Council G1002277Medical Research Council G9439390
6 · The paper itself

Abstract

Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

Indexed as

AdolescentAdultBrainBrain InjuriesCytokinesFemaleHumansInterleukin 1 Receptor Antagonist ProteinMaleMiddle AgedReceptors, Interleukin-1Recombinant ProteinsYoung AdultCytokinesInterleukin 1 Receptor Antagonist ProteinReceptors, Interleukin-1Recombinant Proteins

Identifiers

PMID24569690
PMCPMC4013762
OpenAlexW2092108542

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.