{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:01:44Z","timestamp":1789542104062,"version":"build-2803163510"},"reference-count":43,"publisher":"SAGE Publications","issue":"23","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4\u20138) were included, and all patients received an initial loading dose of 2.5\u2009mg\/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5\u2009mg\/kg\/day whereas the subsequent 6 patients received 10\u2009mg\/kg\/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood\u2013brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.<\/jats:p>","DOI":"10.1089\/neu.2018.6369","type":"journal-article","created":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T08:08:50Z","timestamp":1560845330000},"page":"3253-3263","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Copenhagen Head Injury Ciclosporin Study: A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients"],"prefix":"10.1177","volume":"36","author":[{"given":"Jesper","family":"Kelsen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark."},{"name":"Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden."},{"name":"NeuroVive Pharmaceutical AB, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus J.","family":"Hansson","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden."},{"name":"NeuroVive Pharmaceutical AB, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Yang","sequence":"additional","affiliation":[{"name":"Program for Neurotrauma, Neuroproteomics and Biomarkers Research, Department of Emergency Medicine, University of Florida, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Hugerth","sequence":"additional","affiliation":[{"name":"NeuroVive Pharmaceutical AB, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl-Henrik","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Odense University Hospital, Odense, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"\u00c5strand","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus F.","family":"Keep","sequence":"additional","affiliation":[{"name":"NeuroVive Pharmaceutical AB, Lund, Sweden."},{"name":"Department of Neurosurgery, Sanford Brain and Spine Institute, Sanford Medical Center, Fargo, North Dakota."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Kilbaugh","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania; 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