Intranasal Breast Milk Therapy in HIE (NEO-BRIGHT)

Neonatal Intranasal Breast Milk, Impact on Brain Growth in Hypoxic-ischemic Encephalopathy Therapy (NEO-BRIGHT)

This is an open-label prospective single-center randomized controlled trial to evaluate the effect of intranasal breast milk in hypoxic-ischemic encephalopathic neonates receiving therapeutic hypothermia on long term neurodevelopmental outcome compared to standard care.

Study Overview

• Status: Recruiting
• Conditions: Perinatal Asphyxia; Neonatal Encephalopathy; Neonatal Hypoxic Ischemic Encephalopathy; Hypoxic-Ischaemic 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 open-label prospective randomized controlled single-center interventional study, the objective is to administer fresh, own-mother's breast milk intranasally to neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia, starting from the first day of life and continuing for 28 days.

The primary objective is to compare neurodevelopmental outcomes between the control group and the intervention group receiving intranasal breast milk treatment. The secondary objective is to compare the progression of enteral feeding and the duration of exclusive breastfeeding between the intervention and the control group.

• Study Type: Interventional
• Enrollment (Estimated): 80
• 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
    • Department 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- ischemic 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal breast milk; Fresh own mother's breast milk expressed within 4 hours, will be administered 2 times daily, 0.4 ml in each nostril for 28 days.	Biological: Intranasal breast milk; Own-mother's fresh breast milk (within 4 hours of having been expressed), is administered intranasally to neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia, starting from the first day of life and continuing for 28 days. Dose: 2 times daily, 0.4 ml in each nostril.
No Intervention: Control; Standard care for moderate or severe hypoxic-ischemic encephalopathy with hypothermia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental outcome	The primary outcome will be the 2 year neurodevelopmental outcome comparing standard care and intranasal breast milk therapy groups. The Bayley Scales of Infant Development, Third Edition (Bayley-III) score will be used to assess neurodevelopmental outcome, favorable outcome is defined as having composite scores for cognitive, language and motor scales >85, while adverse outcome is defined as composite scores <80 or death.	2 years

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

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.
• Chen Y, Zhang C, Huang Y, Ma Y, Song Q, Chen H, Jiang G, Gao X. Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway. Adv Drug Deliv Rev. 2024 Apr;207:115196. doi: 10.1016/j.addr.2024.115196. Epub 2024 Feb 7.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: brain; HIE; hypoxic-ischemic encephalopathy; perinatal asphyxia; intranasal breast milk; breast milk stem cells
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Death; Signs and Symptoms, Respiratory; Hypoxia, Brain; Asphyxia; Ischemia; Hypoxia; Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: NNGYK/40202-5/2024

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.-01.01.2030.
• IPD Sharing Access Criteria: On special request pending data transfer agreement approval by Semmelweis University. 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