Clinical trial NCT06747260: Feasibility and Safety of Intranasally Administered Breast Milk in HIE
Official title: Feasibility and Safety of Intranasal Breast Milk in Hypoxic-ischaemic Encephalopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hypoxic Ischaemic Encephalopathy (HIE)
Hypoxic Ischemic Encephalopathy of Newborn
Neonatal Encephalopathy
Neonatal Hypoxic Ischemic Encephalopathy
Brain Injury
Perinatal Asphyxia
Perinatal Asphyxia , Moderate to Severe HIE
Keywords: Hypoxic-ischaemic encephalopathy
Neonatal encephalopathy
Perinatal asphyxia
Breast milk
Breast milk stem cells
Intranasal breast milk
Lead sponsor: Semmelweis University
Sponsor class: OTHER
First posted: 2024-12-24
Enrollment: 10
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective intervention single center study to evaluate the feasibility and safety of intranasal breast milk in hypoxic-ischaemic encephalopathic neonates receiving therapeutic hypothermia.

Detailed description: Perinatal asphyxia and the resulting hypoxic-ischemic encephalopathy (HIE) are the leading cause of neonatal mortality and long-term neurodevelopmental disabilities. Based on our current knowledge, therapeutic hypothermia is the only therapy that has been proven to reduce central nervous system damage in HIE neonates. Improving neurodevelopmental outcomes of newborns with HIE has been an intense area of research over the past decade.

Breast milk is a complex biological substance that contains a variety of bioactive components including neurotrophic growth factors, cytokines, immunoglobulins, and multipotent stem cells. Studies have shown that exclusive breastfeeding in the early stages of development has a positive impact on cognitive outcomes. Animal studies support that mesenchymal stem cells and neurotrophic substances found in breast milk, when administered intranasally enter the central nervous system and reduce the extent of neurological damage. In preterm infants, it has been shown that intranasally administered breast milk is safe and well-tolerated.

In this prospective study our aim is to assess the feasibility and safety of intranasally delivered breast milk to HIE infants treated with hypothermia. Our objective is to administer fresh, own-mother's breast milk intranasally to neonates with HIE starting from the first day of life and continuing for 1 month.

Feasibility will be based on the ability to initiate treatment within 48 hours of birth using own mother's fresh milk expressed within 4 hours and continuing treatment after discharge until day 28. Safety will be assessed through monitoring vital signs and documenting any adverse events. Time to reach full enteral feeding and lengths of exclusive breast feeding will be recorded and analyzed.

Eligibility criteria: Inclusion Criteria:

* Moderate or severe hypoxic- ischaemic encephalopathy, receiving therapeutic hypothermia
* ≥ 35. gestational week
* \< 48 hours of life
* Hypothermia treatment for 72 hours
* Parental consent form

Exclusion Criteria:

* Congenital malformation
* Concurrent cerebral lesions
* ECMO therapy
* Contraindication of lactation
* Mother unable or unwilling to provide fresh breast milk
* Postpartum asphyxia

Primary outcomes:
measure: Proportion of patients where treatment was initiated within 48 hours
timeFrame: 1 months
Secondary outcomes:
measure: Number of adverse events associated with breast milk administration
timeFrame: 1 month
measure: Time to reach full enteral feeding
timeFrame: 1 month
measure: Length of exclusive breast feeding
timeFrame: 2 years
measure: Total number of treatments during first months of life
timeFrame: 1 months
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Division of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
Study officials:
affiliation: Department of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
name: Unoke Meder, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baak LM, Wagenaar N, van der Aa NE, Groenendaal F, Dudink J, Tataranno ML, Mahamuud U, Verhage CH, Eijsermans RMJC, Smit LS, Jellema RK, de Haan TR, Ter Horst HJ, de Boode WP, Steggerda SJ, Prins HJ, de Haar CG, de Vries LS, van Bel F, Heijnen CJ, Nijboer CH, Benders MJNL. Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study. Lancet Neurol. 2022 Jun;21(6):528-536. doi: 10.1016/S1474-4422(22)00117-X.
citation: Hoban R, Gallipoli A, Signorile M, Mander P, Gauthier-Fisher A, Librach C, Wilson D, Unger S. Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage. J Perinatol. 2024 Nov;44(11):1652-1657. doi: 10.1038/s41372-024-01982-8. Epub 2024 Apr 30.
citation: Keller T, Korber F, Oberthuer A, Schafmeyer L, Mehler K, Kuhr K, Kribs A. Intranasal breast milk for premature infants with severe intraventricular hemorrhage-an observation. Eur J Pediatr. 2019 Feb;178(2):199-206. doi: 10.1007/s00431-018-3279-7. Epub 2018 Nov 1.