[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100623857":3},{"organization":4,"outcomesModule":7,"designInfo":71,"detailedDescription":73,"studyPopulation":74,"armGroups":75,"interventions":81,"overallOfficials":70,"centralContacts":87,"locations":97,"responsibleParty":115,"collaborators":117,"id":120,"slug":70,"hasResults":121,"nctId":122,"briefTitle":123,"officialTitle":124,"acronym":125,"eligibilityCriteria":126,"healthyVolunteers":121,"sex":127,"minAge":128,"maxAge":129,"enrollmentInfo":130,"targetDuration":70,"studyType":133,"phases":70,"briefSummary":134,"conditions":135,"keywords":137,"overallStatus":100,"whyStopped":70,"lastUpdateSubmitDate":145,"lastUpdatePostDateStruct":146,"startDateStruct":149,"completionDateStruct":151,"leadSponsor":153,"locationsCount":154},{"fullName":5,"class":6},"Instituto de Investigacion Sanitaria La Fe","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":16,"otherOutcomes":70},[9,13],{"measure":10,"description":11,"timeFrame":12},"Number of participants with treatment-related serious adverse events","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.","From enrollment until term-equivalent age (i.e., up to 40 weeks postmenstrual age)",{"measure":14,"description":15,"timeFrame":12},"Tolerance of donor human milk EV supplementation","Feeding tolerance is evaluated by the number of participants without clinical signs of gastrointestinal symptoms and successful progression of enteral feeding.",[17,21,24,27,31,34,37,40,44,47,50,53,56,60,63,67],{"measure":18,"description":19,"timeFrame":20},"Infant weight","Measurements of weight (grams)","From enrollment until term-equivalent age (weekly) and at 3, 6, 12, 18, and 24 months of corrected age",{"measure":22,"description":23,"timeFrame":20},"Infant length","Measurements of length (cm)",{"measure":25,"description":26,"timeFrame":20},"Infant head circumference","Measurement of head circumference (cm)",{"measure":28,"description":29,"timeFrame":30},"Analysis of redox status biomarkers","Evaluation of the ratio reduced\u002Foxidized glutathione","21 days of life",{"measure":32,"description":33,"timeFrame":30},"Concentration of TFN alpha (inflammatory biomarker)","Evaluation of TFN alpha in plasma employing an Enzyme-Linked Immunosorbent Assay (ELISA) kit (nM)",{"measure":35,"description":36,"timeFrame":30},"Concentration of IL-6 (inflammatory biomarker)","Evaluation of IL-6 in plasma employing an ELISA kit (nM)",{"measure":38,"description":39,"timeFrame":30},"Concentration of calprotectin (inflammation biomarker)","Evaluation of calprotectin in plasma employing an ELISA kit (nM)",{"measure":41,"description":42,"timeFrame":43},"Ratio of meta-tyrosine\u002Fphenylalanine","Evaluation of the ratio of meta-tyrosine\u002Fphenylalanine in urine samples by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS\u002FMS) as an indicator of oxidative damage to proteins","14, 21, and 28 days of life",{"measure":45,"description":46,"timeFrame":43},"Ratio of ortho-tyrosine\u002Fphenylalanine","Evaluation of the ratio of ortho-tyrosine\u002Fphenylalanine in urine samples by LC-MS\u002FMS as an indicator of oxidative damage to proteins",{"measure":48,"description":49,"timeFrame":43},"Ratio of 8-hydroxy-2'-deoxyguanosine\u002F2'-deoxyguanosine","Evaluation of the ratio of 8-hydroxy-2'-deoxyguanosine\u002F2'-deoxyguanosine in urine samples by LC-MS\u002FMS as an indicator of oxidative damage to DNA",{"measure":51,"description":52,"timeFrame":43},"Concentrations of 2,3-dinor-iPF2α-III","Evaluation of 2,3-dinor-iPF2α-III in urine samples by LC-MS\u002FMS as an indicator of oxidative damage to lipids (n mol\u002Fg creatinine)",{"measure":54,"description":55,"timeFrame":43},"Concentrations of 5-iPF2α-VI","Evaluation of 5-iPF2α-VI in urine samples by LC-MS\u002FMS as an indicator of oxidative damage to lipids (n mol\u002Fg creatinine)",{"measure":57,"description":58,"timeFrame":59},"Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) - Motor Composite Score","Motor development will be assessed using the Motor Composite Score of the Bayley-IV. Higher scores indicate better motor development.","6 and 24 months corrected age",{"measure":61,"description":62,"timeFrame":59},"Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) Language Composite Score","Language development will be assessed using the Language Composite Score of the Bayley-IV. Higher scores indicate better language development.",{"measure":64,"description":65,"timeFrame":66},"Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV) - Cognitive Composite Score","Neurodevelopment will be assessed using the Cognitive Composite Score of the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV). Higher scores indicate better cognitive development.","6 and 24 months of corrected age",{"measure":68,"description":69,"timeFrame":66},"Ages and Stages Questionnaire, Third Edition (ASQ-3) Total Score","Developmental screening will be assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3). The ASQ-3 is a parent-completed developmental screening tool consisting of five domains (communication, gross motor, fine motor, problem solving, and personal-social skills). Higher scores indicating better overall development.",null,{"allocation":70,"interventionModel":70,"interventionModelDescription":70,"primaryPurpose":70,"observationalModel":6,"timePerspective":72,"maskingInfo":70},"PROSPECTIVE","Human milk is the optimal source of nutrition for infants, providing essential nutrients and bioactive components that promote growth and development. Very preterm infants (\\\u003C32 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.\n\nExtracellular 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.\n\nThe AdVEMPrem study (PI23\u002F00202, 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\u002Fnitrosative stress. Long-term follow-up will assess sustained effects on growth and neurodevelopmental trajectories.\n\nFindings 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.","Preterm infants at risk of developing necrotizing enterocolitis (NEC), recruited between 14 and 28 days of life during their stay in the Neonatal Intensive Care Unit (NICU). A total of 20 infants will be enrolled to receive oral administration of extracellular vesicles (EVs) isolated from donor human milk (DHM) as a dietary supplement.",[76],{"label":77,"type":70,"description":78,"interventionNames":79},"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.",[80],"Dietary Supplement: Donor human milk extracellular vesicles (DHM-EVs)",[82],{"type":83,"name":84,"description":85,"armGroupLabels":86,"otherNames":70},"DIETARY_SUPPLEMENT","Donor human milk extracellular vesicles (DHM-EVs)","Infants born before 32 weeks of gestation will receive supplementation with extracellular vesicles isolated from donor human milk, in addition to standard nutritional care.",[77],[88,93],{"name":89,"role":90,"phone":91,"phoneExt":70,"email":92},"Julia Kuligowski, PhD","CONTACT","+34961246661","julia.kuligowski@uv.es",{"name":94,"role":90,"phone":95,"phoneExt":70,"email":96},"María Gormaz, PhD, MD","+34\u002F961245686","gormaz_mar@gva.es",[98],{"facility":99,"status":100,"city":101,"state":101,"zip":102,"country":103,"countryCode":104,"cosmosGeoPoint":105,"geoPoint":110,"contacts":111},"Hospital Universitario y Politécnico La Fe","RECRUITING","Valencia","46026","Spain","ES",{"type":106,"coordinates":107},"Point",[108,109],-0.37966,39.47391,{"lat":109,"lon":108},[112,113],{"name":89,"role":90,"phone":91,"phoneExt":70,"email":92},{"name":89,"role":114,"phone":70,"phoneExt":70,"email":70},"PRINCIPAL_INVESTIGATOR",{"type":116,"investigatorFullName":70,"investigatorTitle":70,"investigatorAffiliation":70,"oldNameTitle":70,"oldOrganization":70},"SPONSOR",[118],{"name":119,"class":6},"Hospital Universitario La Fe","100623857",false,"NCT07402083","Administration of Extracellular Vesicles From Donor Human Milk in Preterm Infants","Administration of Extracellular Vesicles Isolated From Donor Human Milk as a Dietary Supplement for the Prevention of Necrotizing Enterocolitis in Preterm Infants","AdVEMPrem","Inclusion Criteria:\n\n* Preterm infants born at \\\u003C32 weeks gestational age\n* Age between 0 and 14 days of life at enrollment\n* At risk of developing necrotizing enterocolitis (NEC)\n* Written informed consent obtained from parent(s) or legal guardian(s)\n\nExclusion Criteria:\n\n* Major congenital anomalies or chromosomal abnormalities\n* Severe gastrointestinal malformations (e.g., gastroschisis, intestinal atresia)\n* Conditions incompatible with enteral feeding or EV supplementation\n* Participation in another interventional clinical trial","ALL","0 Days","14 Days",{"count":131,"type":132},20,"ESTIMATED","OBSERVATIONAL","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.\n\nHuman 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.\n\nIn this study, 20 very preterm infants (\\\u003C32 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.\n\nThe 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.",[136],"Very Preterm Infants (\u003C32 Weeks of Gestation)",[138,139,140,141,142,143,144],"Preterm birth (\u003C32 weeks)","Donor human milk (DHM)","Extracellular vesicles (EVs)","Feeding tolerance","Necrotizing enterocolitis (NEC)","Neurodevelopment","Donor Human Milk Extracellular Vesicle (DHMEVs)","2026-02-09",{"date":147,"type":148},"2026-02-11","ACTUAL",{"date":150,"type":148},"2026-02-05",{"date":152,"type":132},"2029-12-31",{"name":5,"class":6},1]