Hypoxic-Ischaemic EncephalopathyEarly Phase 1NEO-BRIGHTNCT06746532
Intranasal Breast Milk Therapy in HIE
A Early Phase 1 study testing Intranasal breast milk in people with Hypoxic-Ischaemic Encephalopathy and Neonatal Encephalopathy, run by Semmelweis University at 1 site in Hungary.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 48 hours
- Conditions the study is for
- Hypoxic-Ischaemic Encephalopathy, Neonatal Encephalopathy, Perinatal Asphyxia
- What is being tested?
- Intranasal breast milk
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteHungary
- Study dates
- 1 Feb 2025to Dec 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Moderate or severe hypoxic- ischemic encephalopathy, receiving therapeutic hypothermia
- ≥ 35. gestational week < 48 hours of life
- Hypothermia treatment for 72 hours
- Parental consent form
Who cannot join
- Congenital malformation
- Concurrent cerebral lesions
- ECMO therapy
- Contraindication of lactation
- Mother unable or unwilling to provide fresh breast milk
- Postpartum asphyxia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hungary1 site, 1 recruiting
- Recruiting
Department of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
Budapest, 1083
Unoke Meder, MD, PhD, +36303987970, mederunoke@gmail.com
Miklos Szabo, MD, PhD, +36208258221, szabo.miklos@semmelweis.hu
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypoxic-Ischaemic Encephalopathy, Neonatal Encephalopathy, Perinatal Asphyxia, Neonatal Hypoxic Ischemic Encephalopathy
- Being tested
- Intranasal breast milk
- Keywords
- HIE, intranasal breast milk, perinatal asphyxia, brain, breast milk stem cells, hypoxic-ischemic encephalopathy
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal breast milkBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Standard care for moderate or severe hypoxic-ischemic encephalopathy with hypothermia. |
| Intranasal breast milk | Experimental | 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. Receives: Biological: Intranasal breast milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (2)
Time to reach full enteral feeding
Time to reach full enteral feeding will be recorded and analyzed as a secondary outcome.
Measured: 1 month
Length of exclusive breast feeding
Lengths of exclusive breast feeding will be recorded and analyzed as a secondary outcome.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2024
- Study start1 Feb 2025 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischaemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Unoke Meder, MD, PhD, Principal investigator, Department of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06746532
- Sponsor's protocol ID
- NNGYK/40202-5/2024
- Acronym
- NEO-BRIGHT
- Status last verified
- Dec 2024
- First submitted
- 16 Dec 2024
- Last updated
- 24 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: On special request pending data transfer agreement approval by Semmelweis University.
Publications
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.
PubMed 38336090Baak 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.
PubMed 35568047Hoban 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.
PubMed 38688998Keller 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.
PubMed 30386923
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neonatal Intranasal Breast Milk, Impact on Brain Growth in Hypoxic-ischemic Encephalopathy Therapy (NEO-BRIGHT)
- ClinicalTrials.gov ID
- NCT06746532
- Acronym / sponsor ID
- NEO-BRIGHT / NNGYK/40202-5/2024
- Conditions
- Hypoxic-Ischaemic Encephalopathy, Neonatal Encephalopathy, Perinatal Asphyxia, Neonatal Hypoxic Ischemic Encephalopathy
- Keywords
- HIE, intranasal breast milk, perinatal asphyxia, brain, breast milk stem cells, hypoxic-ischemic encephalopathy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Study start
- 1 Feb 2025 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 24 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Standard care for moderate or severe hypoxic-ischemic encephalopathy with hypothermia. |
| Intranasal breast milk | Experimental | Biological: Intranasal breast milkFresh own mother's breast milk expressed within 4 hours, will be administered 2 times daily, 0.4 ml in each nostril for 28 days. |
Who may qualify
- Ages
- Up to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Moderate or severe hypoxic- ischemic encephalopathy, receiving therapeutic hypothermia
- ≥ 35. gestational week < 48 hours of life
- Hypothermia treatment for 72 hours
- Parental consent form
Key exclusion criteria (6 listed)
- Congenital malformation
- Concurrent cerebral lesions
- ECMO therapy
- Contraindication of lactation
- Mother unable or unwilling to provide fresh breast milk
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intranasal breast milkOwn-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. | Biological | Intranasal breast milk |
Primary outcome
Neurodevelopmental outcome
Time frame: 2 years
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 secondary outcomes
Time to reach full enteral feeding
Time frame: 1 month
Length of exclusive breast feeding
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Background: PubMed 38336090Chen 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.
- Background: PubMed 35568047Baak 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.
- Background: PubMed 38688998Hoban 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.
- Background: PubMed 30386923Keller 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.
- Individual participant dataSharing planned: Yes. On special request pending data transfer agreement approval by Semmelweis University.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Unoke Meder, MD, PhD principal investigator
Department of Neonatology, Pediatric Center, Semmelweis University, Budapest, Hungary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Intranasal breast milk in people with Hypoxic-Ischaemic Encephalopathy and Neonatal Encephalopathy, run by Semmelweis University at 1 site in Hungary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Unoke Meder, MD, PhD (+36303987970, mederunoke@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurodevelopmental outcome (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06746532, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2024.