Administration of Extracellular Vesicles Isolated From Donor Human Milk as a Dietary Supplement for the Prevention of Necrotizing Enterocolitis in Preterm Infants
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related serious adverse events
研究概览
简要总结
The AdVEMPrem study is exploring whether tiny particles called extracellular vesicles (EVs), which are naturally found in human milk, can help protect very premature babies from serious gut problems such as necrotizing enterocolitis (NEC). NEC is a dangerous condition that affects the intestines of preterm infants and can lead to long-term health issues.
Human milk is the best nutrition for babies, but when a mother's own milk is not available, donor human milk (DHM) is used. EVs in milk carry proteins, fats, and genetic material that may support gut development, immunity, and brain growth. While laboratory studies suggest EVs are beneficial, their effects in premature babies have not yet been proven.
In this study, 20 very preterm infants (<32 weeks of gestation) will be enrolled during their stay in the Neonatal Intensive Care Unit (NICU). All babies in the study will receive oral supplementation with EVs isolated from donor human milk. Researchers will monitor feeding tolerance, growth, intestinal health, and early development. Blood and urine samples will also be collected to study how EVs affect metabolism and stress markers.
The main goal is to see if EV supplementation is safe and well tolerated. Longer-term follow-up will explore whether EVs improve growth and neurodevelopment as the babies grow. This research could lead to new nutritional strategies to reduce NEC and improve outcomes for premature infants and their families.
详细描述
Human milk is the optimal source of nutrition for infants, providing essential nutrients and bioactive components that promote growth and development. Very preterm infants (<32 weeks gestation) are particularly vulnerable to feeding intolerance, impaired growth, and severe complications such as necrotizing enterocolitis (NEC). When a mother's own milk is insufficient or unavailable, pasteurized donor human milk (DHM) is the recommended alternative.
Extracellular vesicles (EVs) are nanosized particles naturally present in human milk that carry proteins, lipids, and nucleic acids involved in cell signaling, intestinal maturation, immune regulation, and neurodevelopment. Preclinical studies suggest that milk-derived EVs may reduce inflammation and support gut and brain development, but their role in clinical outcomes for very preterm infants has not yet been established.
The AdVEMPrem study (PI23/00202, ISCIII) is a prospective, single-arm pilot trial designed to evaluate the tolerance and safety of DHM-derived EV supplementation in very preterm infants. All enrolled infants will receive oral EV supplementation during hospitalization in the Neonatal Intensive Care Unit. Protocols for isolation and quality control of DHM-EVs will be established to ensure reproducible yields. The biochemical composition of milk and EVs will be characterized for product characterization and exploratory analyses, with emphasis on lipid profiles and functional properties. These analyses are not participant-level outcome measures. Clinical, nutritional, and developmental parameters will be monitored during the neonatal period, alongside biomarkers of redox balance and oxidative/nitrosative stress. Long-term follow-up will assess sustained effects on growth and neurodevelopmental trajectories.
Findings from this pilot study will provide foundational evidence for the potential of milk-derived EVs as a safe nutritional strategy to prevent NEC and improve outcomes in preterm infants. Results will inform the design of larger multicenter trials and may contribute to the development of standardized EV-based supplements or analogues from alternative sources, thereby addressing variability in donor milk composition. Ultimately, access to an efficient and safe nutritional supplement could reduce the incidence of NEC, improve infant and family outcomes, and deliver socio-economic and ecological benefits.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Days 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants born at <32 weeks gestational age
- •Age between 0 and 14 days of life at enrollment
- •At risk of developing necrotizing enterocolitis (NEC)
- •Written informed consent obtained from parent(s) or legal guardian(s)
排除标准
- •Major congenital anomalies or chromosomal abnormalities
- •Severe gastrointestinal malformations (e.g., gastroschisis, intestinal atresia)
- •Conditions incompatible with enteral feeding or EV supplementation
- •Participation in another interventional clinical trial
研究组 & 干预措施
EV supplementation in very preterm infants
Infants born before 32 weeks of gestation will receive own mother's milk supplemented with extracellular vesicles isolated from donor human milk.
干预措施: Donor human milk extracellular vesicles (DHM-EVs) (Dietary Supplement)
结局指标
主要结局
Number of participants with treatment-related serious adverse events
时间窗: From enrollment until term-equivalent age (i.e., up to 40 weeks postmenstrual age)
Safety will be evaluated by the number of participants experiencing one or more treatment-related serious adverse events, defined as any of the following: (i) necrotizing enterocolitis (Bell stage ≥ II); (ii) metabolic or renal complications requiring medical intervention, (iii) cholestasis, or (iv) culture-proven sepsis. Participants experiencing multiple events will be counted once.
Tolerance of donor human milk EV supplementation
时间窗: From enrollment until term-equivalent age (i.e., up to 40 weeks postmenstrual age)
Feeding tolerance is evaluated by the number of participants without clinical signs of gastrointestinal symptoms and successful progression of enteral feeding.
次要结局
- Infant weight(From enrollment until term-equivalent age (weekly) and at 3, 6, 12, 18, and 24 months of corrected age)
- Infant length(From enrollment until term-equivalent age (weekly) and at 3, 6, 12, 18, and 24 months of corrected age)
- Infant head circumference(From enrollment until term-equivalent age (weekly) and at 3, 6, 12, 18, and 24 months of corrected age)
- Analysis of redox status biomarkers(21 days of life)
- Concentration of TFN alpha (inflammatory biomarker)(21 days of life)
- Concentration of IL-6 (inflammatory biomarker)(21 days of life)
- Concentration of calprotectin (inflammation biomarker)(21 days of life)
- Ratio of meta-tyrosine/phenylalanine(14, 21, and 28 days of life)
- Ratio of ortho-tyrosine/phenylalanine(14, 21, and 28 days of life)
- Ratio of 8-hydroxy-2'-deoxyguanosine/2'-deoxyguanosine(14, 21, and 28 days of life)
- Concentrations of 2,3-dinor-iPF2α-III(14, 21, and 28 days of life)
- Concentrations of 5-iPF2α-VI(14, 21, and 28 days of life)
- Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) - Motor Composite Score(6 and 24 months corrected age)
- Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) Language Composite Score(6 and 24 months corrected age)
- Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) - Cognitive Composite Score(6 and 24 months of corrected age)
- Ages and Stages Questionnaire, Third Edition (ASQ-3) Total Score(6 and 24 months of corrected age)