Human amnion cells for the prevention of bronchopulmonary dysplasia: a protocol for a phase I dose escalation study
Human amnion cells for the prevention of bronchopulmonary dysplasia: a protocol for a phase I dose escalation study
复制标题
DOI：
10.1136/bmjopen-2018-026265
复制
发表时间：
2019-06-01
期刊：
影响因子：
2.9
通讯作者：
Wallace, Euan M.
中科院分区：
文献类型：
--
作者：
Baker, Elizabeth Kate;Malhotra, Atul;Wallace, Euan M.
支气管肺发育不良（BPD）是早产的重要后遗症，与长期肺功能异常和不良神经发育结局相关。炎症反应、继发性分隔抑制和血管发育不良在BPD的发病机制中起重要作用。人羊膜上皮细胞（hAEC），来源于胎盘组织的干细胞样细胞，能够调节炎症环境，并且在BPD样损伤的临床前研究中，能够恢复肺结构和功能。同种异体hAEC可能会提出一个新的预防和修复治疗BPD.Methods和分析在这两个中心，I期细胞剂量递增的研究，我们将评估静脉注射hAEC输注在早产儿严重BPD的高风险的安全性。24名出生于妊娠不到29周的婴儿将从生命的第14天开始接受静脉注射hAEC。我们将单次静脉内hAEC输注中所含的细胞剂量从200万个细胞/kg递增至1000万个细胞/kg。进一步的剂量递增将通过以5天间隔给予的重复输注来实现，最大总剂量为3000万个细胞/kg（三次输注）。安全性是主要结局。婴儿将随访至2岁矫正年龄。其他结果指标包括hAEC输注后婴儿细胞因子谱的描述，呼吸结果包括BPD和肺动脉高压以及其他新生儿发病率，包括2年时的神经发育评估。伦理和传播本研究于2018年6月12日获得莫纳什健康和莫纳什大学人类研究伦理委员会的批准。招聘工作于2018年8月开始，预计需要18个月。因此，后续工作将于2022年年中完成。本研究的结果将通过同行评审期刊和会议进行传播。方案第5版，2018年5月21日。
Introduction Bronchopulmonary dysplasia (BPD), an important sequela of preterm birth, is associated with long-term abnormalities of lung function and adverse neurodevelopmental outcomes. Inflammation, inhibition of secondary septation and vascular maldevelopment play key roles in the pathogenesis of BPD. Human amnion epithelial cells (hAECs), stem-like cells, derived from placental tissues are able to modulate the inflammatory milieu and, in preclinical studies of BPD-like injury, restore lung architecture and function. Allogeneic hAECs may present a new preventative and reparative therapy for BPD.Methods and analysis In this two centre, phase I cell dose escalation study we will evaluate the safety of intravenous hAEC infusions in preterm infants at high risk of severe BPD. Twenty-four infants born at less than 29 weeks' gestation will each receive intravenous hAECs beginning day 14 of life. We will escalate the dose of cells contained in a single intravenous hAEC infusion in increments from 2 million cells/kg to 10 million cells/kg. Further dose escalation will be achieved with repeat infusions given at 5 day intervals to a maximum total dose of 30 million cells/kg (three infusions). Safety is the primary outcome. Infants will be followed-up until 2 years corrected age. Additional outcome measures include a description of infants' cytokine profile following hAEC infusion, respiratory outcomes including BPD and pulmonary hypertension and other neonatal morbidities including neurodevelopmental assessment at 2 years.Ethics and dissemination This study was approved on the June12th, 2018 by the Human Research Ethics Committee of Monash Health and Monash University. Recruitment commenced in August 2018 and is expected to take 18 months. Accordingly, follow-up will be completed mid-2022. The findings of this study will be disseminated via peer-reviewed journals and at conferences.Protocol version 5, 21 May 2018.