{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:57Z","timestamp":1787017077941,"version":"build-2736575974"},"reference-count":22,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Collaboration Programme, an NHS England and National Institute for Health Research partnership","award":["NIHR127963"],"award-info":[{"award-number":["NIHR127963"]}]},{"DOI":"10.13039\/100013786","name":"Cure EB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,4,30]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic mucocutaneous fragility disorder characterised by chronic blistering, slow wound healing and increased risk of squamous cell carcinoma. Current management options are very limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This is a randomised (1:1), placebo-controlled, double-blinded crossover (A\/B) trial with an internal phase I dose de-escalation (4+5 design) in the first 3 months and a 12-month continued treatment follow-on open-label study if 3-month outcome data from the crossover trial indicate safe and beneficial effects. RDEB is a rare condition, so we expect to recruit a maximum of 36 participants based on feasibility and not formal power considerations. Participants aged&gt;6 months and &lt;16 years will be recruited at Great Ormond Street Hospital and Birmingham Children\u2019s Hospital. They will receive 2\u20133\u00d710\n                      <jats:sup>6<\/jats:sup>\n                      cells\/kg intravenous infusion of umbilical cord-derived mesenchymal stem cells or placebo at the start of each crossover period (day 0) and 14 days later. The dose will be de-escalated to 1\u20131.5\u00d710\n                      <jats:sup>6<\/jats:sup>\n                      cells\/kg depending on observed toxicity. For the main crossover trial, the primary outcome is the change in disease severity as measured by the Epidermolysis Bullosa Disease Activity and Scarring Index at 3 months from day 0 infusion. Secondary outcomes measured at 3 and 6 months from day 0 infusion include changes in general clinical appearance of skin disease, pain and itch, and quality of life. Adverse events and serious adverse events will be monitored throughout the trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>North East\u2014York Research Ethics Committee approved the protocol (ref: 21\/NE\/0016) on 16 March 2021. Findings will be published in peer-reviewed scientific journals, presented at relevant national and international conferences, and an open-access final report submitted to the funder.<\/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=\"ISRCTN14409785\">ISRCTN14409785<\/jats:ext-link>\n                      . Protocol V. 8.0, 14 November 2022.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-089857","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T15:49:29Z","timestamp":1747842569000},"page":"e089857","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Mesenchymal intravenous stromal cell infusions in children with recessive dystrophic epidermolysis bullosa: MissionEB protocol for a randomised, double-blinded, placebo-controlled, two-centre, crossover trial with an internal phase I dose de-escalation phase and open-label extension"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"isrctn14409785","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-7923","authenticated-orcid":false,"given":"Maria L","family":"Bageta","sequence":"first","affiliation":[{"name":"Department of Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-719X","authenticated-orcid":false,"given":"Pablo","family":"L\u00f3pez-Balboa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-6920","authenticated-orcid":false,"given":"Munyaradzi","family":"Dimairo","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, ScHARR, The University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-3354","authenticated-orcid":false,"given":"Rachel","family":"Glover","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, ScHARR, The University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-2844","authenticated-orcid":false,"given":"Kate","family":"Hutchence","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, ScHARR, The University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6259-0822","authenticated-orcid":false,"given":"Diana","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, ScHARR, The University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Cooper","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, ScHARR, The University of Sheffield, Sheffield, 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