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Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial

INTRODUCTION: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in ne...

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Autores principales: Matsuyama, Nao, Shimizu, Shinobu, Ueda, Kazuto, Suzuki, Toshihiko, Suzuki, Sakiko, Miura, Ryosuke, Katayama, Akemi, Ando, Masahiko, Mizuno, Masaaki, Hirakawa, Akihiro, Hayakawa, Masahiro, Sato, Yoshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045108/
https://www.ncbi.nlm.nih.gov/pubmed/35473726
http://dx.doi.org/10.1136/bmjopen-2021-057073
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author Matsuyama, Nao
Shimizu, Shinobu
Ueda, Kazuto
Suzuki, Toshihiko
Suzuki, Sakiko
Miura, Ryosuke
Katayama, Akemi
Ando, Masahiko
Mizuno, Masaaki
Hirakawa, Akihiro
Hayakawa, Masahiro
Sato, Yoshiaki
author_facet Matsuyama, Nao
Shimizu, Shinobu
Ueda, Kazuto
Suzuki, Toshihiko
Suzuki, Sakiko
Miura, Ryosuke
Katayama, Akemi
Ando, Masahiko
Mizuno, Masaaki
Hirakawa, Akihiro
Hayakawa, Masahiro
Sato, Yoshiaki
author_sort Matsuyama, Nao
collection PubMed
description INTRODUCTION: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates. METHODS AND ANALYSIS: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C–34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences. TRIAL REGISTRATION NUMBERS: NCT04261335, jRCT2043190112.
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spelling pubmed-90451082022-05-11 Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial Matsuyama, Nao Shimizu, Shinobu Ueda, Kazuto Suzuki, Toshihiko Suzuki, Sakiko Miura, Ryosuke Katayama, Akemi Ando, Masahiko Mizuno, Masaaki Hirakawa, Akihiro Hayakawa, Masahiro Sato, Yoshiaki BMJ Open Paediatrics INTRODUCTION: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates. METHODS AND ANALYSIS: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C–34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences. TRIAL REGISTRATION NUMBERS: NCT04261335, jRCT2043190112. BMJ Publishing Group 2022-04-25 /pmc/articles/PMC9045108/ /pubmed/35473726 http://dx.doi.org/10.1136/bmjopen-2021-057073 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Paediatrics
Matsuyama, Nao
Shimizu, Shinobu
Ueda, Kazuto
Suzuki, Toshihiko
Suzuki, Sakiko
Miura, Ryosuke
Katayama, Akemi
Ando, Masahiko
Mizuno, Masaaki
Hirakawa, Akihiro
Hayakawa, Masahiro
Sato, Yoshiaki
Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title_full Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title_fullStr Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title_full_unstemmed Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title_short Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
title_sort safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (shield trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial
topic Paediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045108/
https://www.ncbi.nlm.nih.gov/pubmed/35473726
http://dx.doi.org/10.1136/bmjopen-2021-057073
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