{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:53:02Z","timestamp":1793641982406,"version":"4.5.1"},"reference-count":22,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T044802\/1"],"award-info":[{"award-number":["MR\/T044802\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000589","name":"Chief Scientist Office","doi-asserted-by":"publisher","award":["Centre for Precision Cell Therapy for the Liver \/"],"award-info":[{"award-number":["Centre for Precision Cell Therapy for the Liver \/"]}],"id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,11,4]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute liver failure (ALF) has no effective treatment other than liver transplantation and is commonly caused by paracetamol overdose. New treatments are needed to treat and prevent ALF. Alternatively-activated macrophages (AAMs) can promote resolution of liver necrosis and stimulate hepatocyte proliferation. Using AAMs in unscheduled care requires the use of an allogeneic product. A clinical trial is needed to determine the safety and tolerability of allogeneic AAMs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A single-centre, open-label, dose-escalation, phase 1 randomised trial to determine whether there is dose-limiting toxicity of AAMs in patients with paracetamol-induced acute liver injury. Randomisation will occur at higher doses. Between 17 and 30 patients will receive treatment, subject to dose-limiting toxicity and an adaptive trial design which aims to reduce the risk of allocation bias through blinding and randomisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by North East\u2014York Research Ethics Committee (reference 23\/NE\/0019), National Health Service Lothian Research and Development department, and the UK Medicines and Healthcare products Regulatory Agency. When the trial concludes, results will be shared by presentation and publication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN12637839\">ISRCTN12637839<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-089417","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T21:26:24Z","timestamp":1733779584000},"page":"e089417","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Macrophage Therapy for Acute Liver Injury (MAIL): a study protocol for a phase 1 randomised, open-label, dose-escalation study to evaluate safety, tolerability and activity of allogeneic alternatively activated macrophages in patients with paracetamol-induced acute liver injury in the UK"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"isrctn12637839","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-2603","authenticated-orcid":false,"given":"Christopher","family":"Humphries","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melisande","family":"Addison","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruprasad","family":"Aithal","sequence":"additional","affiliation":[{"name":"MAIL Trial Data Monitoring Committee, Edinburgh 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