The Pilot Experimental Study of the Neuroprotective Effects of Exosomes in Extremely Low Birth Weight Infants
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Occurrence and rate of dose limiting toxicity
研究概览
简要总结
To study the safety and efficacy of intranasal administration of exosomes derived from mesenchymal stromal cells on long-term neurodevelopmental outcome in extremely low birth weight infants born at gestational age 25/0-27/6 weeks.
详细描述
Surviving extremely low birth weight (ELBW) infants are at risk of severe neurodevelopmental disability. Exosomes or extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) can mediate a variety of different effects, including synaptic plasticity, nutritional metabolic support, nerve regeneration, inflammatory response, anti-stress effect, cellular waste disposal, treating neurological injury, preventing hemorrhagic and ischemic brain lesions, playing an important role in health and neuroprotection in extremely premature newborns during neonatal intensive care.
The proposed blinded randomized controlled trial was designed to compare the effect of intranasal administration of exosomes on long-term neurodevelopmental outcome in ELBW infants.
ELBW infants will be randomized to receive (group 1) and not receive exosomes (control group).
Group 1 - Neonates will receive exosomes (1 dose will be obtained from a daily conditioned culture medium of 120 million MSCs) suspended in 500 µl of phosphate buffer in each nostril at 50 µl with an interval of 2-3 minutes. The therapeutic course will consist of 5 instillations with an interval of 1 days.
The primary outcome measure is the incidence of death, the incidence of survival with any of either severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), or brain injury on cranial ultrasound and MRI or major neurodevelopmental impairment determined at 36 months of age corrected for prematurity (where major neurodevelopmental impairment is defined as any of the following: cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Cognitive delay defined as mental developmental index (MDI) score of the Griffiths-II and Bayley Scales of Infant Development (2nd edition) < 85, cerebral palsy, or severe visual or hearing impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 1 Day 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Premature newborns of gestational age (GA) 25/0-27/6 weeks,
排除标准
- •Missing written parental consent
- •Damages to the nasal mucosa
- •Maxillofacial defects
- •Major congenital anomalies (including chromosomal aberrations, cyanotic congenital heart defects, syndromes likely affecting long-term outcome, and major congenital malformations requiring surgical correction during newborn period)
- •Infants who died before 48 hours, infants in whom the clinical decision to withhold intensive care was made, infants who were not considered viable
- •Infants with edematous hemolytic disease of newborns, non-immune fetal dropsy,
- •Multifetal Gestations
- •Participation in another study with ongoing use of an unlicensed investigational product from 28 days before study enrollment until the end of the study
结局指标
主要结局
Occurrence and rate of dose limiting toxicity
时间窗: Up to 1 week following after intranasal administration of EVs
Dose limiting toxicity consists of the following events: Death occurring within 24 hours after intranasal administration of EVs; Hypersensitivity / anaphylactic to EVs defined as any severe systemic inflammatory response syndrome with negative blood culture not consistent with the overall clinical course of the infant occurring within 72 hours after intranasal administration of EVs; Any other serious adverse event not expected in this patient population for which there is no alternative explanation but the administration of EVs, occurring within 1 week of injection.
次要结局
- Changes in Hemodynamics(Time Frame: At enrollment, 48 hours following intranasal administration of EVs, 28 days of life, and 36 weeks corrected gestational age)
- Feasibility: Recruitment Timing(Day of life 1-10)
- Feasibility: Participant Retainment(From enrollment until follow-up at 18-36 months-of-age)
- Long-term Safety Follow-Up(3 years following follow-up visit)
- Rate of death(From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first))
- Occurrence of Other Severe Complications of Prematurity(From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first))
- Need for Ventilatory Support(From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first))
- Feasibility: Administration(Day of life 1-10)
- Feasibility: Recruitment Efficiency(Day of life 1-10)
- Griffiths-II and Bayley Scales of Infant Development (2nd edition)(18-36 months-of-age)