脐带华通氏胶间充质基质细胞血管内给药对创伤性脑损伤后全身免疫调节和神经炎症的影响（TRAUMACELL）：一项多中心随机对照试验的研究方案

Effects of intravascular administration of mesenchymal stromal cells derived from Wharton's Jelly of the umbilical cord on systemic immunomodulation and neuroinflammation after traumatic brain injury (TRAUMACELL): study protocol for a multicentre randomised controlled trial.

作者信息

Sigaut Stéphanie, Tardivon Coralie, Jacquens Alice, Bottlaender Michel, Gervais Philippe, Habert Marie-Odile, Monsel Antoine, Roquilly Antoine, Boutonnet Mathieu, Galanaud Damien, Cras Audrey, Boucher-Pillet Hélène, Florence Aline-Marie, Cavalier Ines, Menasche Philippe, Degos Vincent, Couffignal Camille

机构信息

Anesthesiology and Intensive Care, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, Île-de-France, France

NeuroDiderot, Neuroprotection of the Developing Brain, Université Paris Cité, INSERM, Paris, Île-de-France, France.

出版信息

BMJ Open. 2024 Dec 31;14(12):e091441. doi: 10.1136/bmjopen-2024-091441.

DOI:10.1136/bmjopen-2024-091441

PMID:39740941

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11749534/

Abstract

INTRODUCTION

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Treatments for TBI patients are limited and none has been shown to provide prolonged and long-term neuroprotective or neurorestorative effects. A growing body of evidence suggests a link between TBI-induced neuro-inflammation and neurodegenerative post-traumatic disorders. Consequently, new therapies triggering immunomodulation and promoting neurological recovery are the subject of major research efforts. We hypothesise that repeated intravenous treatment with mesenchymal stromal cells derived from Wharton's Jelly of the umbilical cord-derived mesenchymal stromal cells ((WJ-UC-MSC) may be associated with a significant decrease of post-TBI neuroinflammation and improvement of neurological status.

METHODS AND ANALYSIS

The TRAUMACELL trial is a prospective, national multicentre, phase III, superiority, double-arm comparative randomised (1:1) double-blinded clinical trial. Among patients aged between 18-50, with a severe TBI defined by a Glasgow score less than 12 (within the first 48 hours) with brain traumatic lesion on CT Scan and needing intracranial pressure monitoring, with no other significant organ trauma (abbreviated injury scale<2) and unresponsive to verbal commands after 5 days of sedation discontinuation, 68 will be randomly allocated to receive either WJ-UC-MSC solution or placebo, with three intravenous injections 1 week apart. The primary outcome is the [F]-DPA-714 signal intensity in corpus callosum measured by dynamic positron emission tomography (PET)-MRI at 6 months after the last injection, blinded to the randomisation arm, to evaluate the post-traumatic neuro-inflammation.

ETHICS AND DISSEMINATION

The TRAUMACELL trial has been approved by an independent ethics committee (CPP SUD EST II) and French Medicines Agency (2023-504415-33-00) for all study centres. Participant recruitment will be starting in September 2024. Results will be published in international peer-reviewed medical journals.

TRIAL REGISTRATION NUMBER

NCT06146062, first posted 24 November 2023 PROTOCOL VERSION IDENTIFIER: TRAUMACELL-V.2.0_20240102.

摘要

引言

创伤性脑损伤（TBI）是全球范围内死亡和残疾的主要原因之一。TBI患者的治疗方法有限，且尚无任何一种治疗方法被证明能提供长期的神经保护或神经修复作用。越来越多的证据表明，TBI诱导的神经炎症与创伤后神经退行性疾病之间存在联系。因此，触发免疫调节并促进神经恢复的新疗法是主要研究工作的主题。我们假设，重复静脉注射源自脐带华通氏胶的间充质基质细胞（WJ-UC-MSC）可能与TBI后神经炎症的显著减轻和神经状态的改善有关。

方法与分析

TRAUMACELL试验是一项前瞻性、全国多中心、III期、优效性、双臂比较随机（1:1）双盲临床试验。在年龄在18至50岁之间、格拉斯哥评分低于12分（在最初48小时内）、CT扫描显示有脑外伤病变且需要颅内压监测、无其他重大器官创伤（简明损伤定级<2）且在停用镇静剂5天后对言语指令无反应的患者中，68名患者将被随机分配接受WJ-UC-MSC溶液或安慰剂，每隔1周进行三次静脉注射。主要结局是在最后一次注射后6个月，通过动态正电子发射断层扫描（PET）-MRI测量胼胝体中的[F]-DPA-714信号强度，对随机分组情况设盲，以评估创伤后神经炎症。