Feasibility and Safety of Intranasally Administered Breast Milk in HIE (F-NEO-BRIGHT)

Feasibility and Safety of Intranasal Breast Milk in Hypoxic-ischaemic Encephalopathy

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Injury; Perinatal Asphyxia; Neonatal Encephalopathy; Perinatal Asphyxia , Moderate to Severe HIE; Hypoxic Ischemic Encephalopathy of Newborn; Hypoxic Ischaemic Encephalopathy (HIE); Neonatal Hypoxic Ischemic Encephalopathy
• Intervention / Treatment: Biological: Intranasal breast milk

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Unoke Meder, MD, PhD; Phone Number: +36303987970; Email: mederunoke@gmail.com
• Study Contact Backup: Name: Agnes Jermendy, MD, PhD; Phone Number: +36204600798; Email: jermendy@gmail.com

Study Locations

• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • Division of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
    • Contact: Unoke Meder, MD, PhD; Phone Number: +36303987970; Email: mederunoke@gmail.com
    • Contact: Miklos Szabo, MD, PhD; Phone Number: +36208258221; Email: szabo.miklos@semmelweis.hu
    • Principal Investigator: Unoke Meder, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal breast milk; Study participants receive their own mother's fresh breast milk, expressed within 4 hours, administered 2 times daily, 0.4 ml in each nostril for 28 days.	Biological: Intranasal breast milk; Neonates with hypoxic-ischemic encephalopathy receive their own-mother's fresh breast milk intranasally, starting from the first 48 hours of life and continuing for 28 days. Dose: 2 times daily, 0.4 ml in each nostril (15 minutes apart).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients where treatment was initiated within 48 hours	Feasibility will be based on the ability to initiate treatment within 48 hours of birth using own mother's fresh milk.	1 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach full enteral feeding	Time to reach full enteral feeding will be recorded and analyzed as a secondary outcome.	1 month
Length of exclusive breast feeding	Lengths of exclusive breast feeding will be recorded and analyzed as a secondary outcome.	2 years
Number of adverse events associated with breast milk administration	Number of adverse events associated with breast milk administration will be recorded, including desaturation (SpO2<80%), bradycardia (heart rate <70% of baseline), apneic episode requiring bag and mask ventilation within 5 minutes of the intervention, or an increase in respiratory support (mode, setting, or FiO2 increase >10%) within 1 hour of the intervention.	1 month
Total number of treatments during first months of life	Total number of treatments administered in hospital and at home during the first months of life	1 months

Collaborators and Investigators

• Sponsor: Semmelweis University
• Investigators: Principal Investigator: Unoke Meder, MD, PhD, Department of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2024
• Primary Completion (Estimated): September 22, 2025
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Perinatal asphyxia; Breast milk; Neonatal encephalopathy; Hypoxic-ischaemic encephalopathy; Breast milk stem cells; Intranasal breast milk
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Infant, Newborn, Diseases; Death; Signs and Symptoms, Respiratory; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia, Brain; Asphyxia; Ischemia; Hypoxia; Brain Injuries; Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Asphyxia Neonatorum
• Other Study ID Numbers: SE-NEONAT-03/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On special request pending data transfer agreement approval by Semmelweis University.
• IPD Sharing Time Frame: 20.12.2024.-01.01.2026.
• IPD Sharing Access Criteria: Sharing upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No