Intranasal Human Milk for Intraventricular Hemorrhage

NCT ID: NCT04225286

Last Updated: 2022-05-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-11
• Study Completion Date: 2023-12-31

Brief Summary

Intraventricular hemorrhage (IVH) is a leading cause of brain injury in infants born before term. Severe IVH, which occurs nearly exclusively in very preterm infants (born before 32 weeks gestation) who are already at risk of neurodevelopmental delays and cerebral palsy at baseline, results in a ~5 times higher risk of death or moderate-severe neurodevelopmental impairment, as well as short-term morbidities in the neonatal intensive care unit (NICU). Infants with grade I and II IVH, although less severe than the higher grades of IVH, also have a higher risk of death or moderate to severe neurodevelopmental impairment compared to infants with a normal head ultrasound. Outcomes are worsened by the fact that the brains of these preterm infants are not fully developed, so the progenitor cells that would later differentiate and mature are damaged, resulting in hypomyelination and gray matter loss that are associated with poor neurodevelopmental outcomes. There is no available therapy to treat the IVH or resultant brain injury, other than symptomatic management for resultant post-hemorrhagic hydrocephalus with lumbar punctures and temporary or permanent shunts, which have significant risks on their own.

This is a phase I trial to determine whether fresh intranasal human milk (HM) can be safely delivered as stem cell therapy to preterm IVH patients within a 3-hour window from HM expression and to identify signals which would indicate whether intranasal HM stimulates the repair of damaged brain tissue. Outcomes will be compared to HM fed historical IVH controls. Recruitment will take place in tertiary care NICUs in Toronto, which care for the highest proportion of very preterm infants with IVH in Canada. These NICUs have already adopted a common protocolized approach to manage severe IVH and post-hemorrhagic hydrocephalus with intensive monitoring, early symptomatic management, and detailed prospectively collected IVH data.

Conditions

Intraventricular Hemorrhage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intranasal human breast milk

Human breast milk delivered intranasally to preterm infants (<33 weeks gestation at birth, stratified < and ≥28 weeks) with any grade IVH/intraparenchymal hemorrhage/infarction identified on head ultrasound in the first 10 days of life.

Dosing: Escalating dose starting at 0.2mL into one nostril with repeat dose 10-15 minutes later 1-2x daily, depending on availability of fresh HM

Group Type: EXPERIMENTAL

Human breast milk

Intervention Type: OTHER

Intranasal human breast milk

Interventions

Human breast milk

Intranasal human breast milk

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Preterm infants (<33 weeks gestation at birth, stratified < and ≥28 weeks) with any grade IVH/intraparenchymal hemorrhage/infarction on head ultrasound in the first 10 days of life. Diagnostic criteria will be based on the Papile definitions as used by the study sites/Toronto Centre for Neonatal Health for PHVD management, outlined in the document "Intraventricular Hemorrhage and Measurements of Lateral Ventricular Size from Head Ultrasound"

Exclusion Criteria

1. Disorders associated with neurodevelopmental delays or impairment (i.e. Trisomy 21)

2. Moribund/critically ill infant or known lethal diagnosis with plans by medical team to redirect care

3. Choanal atresia or anomalies that would not allow intranasal treatment

4. Surgical condition (e.g. esophageal atresia) for which team feels intranasal HM is contraindicated

5. Enrolled in other intervention trials in which primary target is neurodevelopmental outcome

6. Parent with lactation contraindication(s) (i.e. HIV) or parent who declines lactation initiation

7. Lactating parent unable to provide fresh HM: unable/unwilling to pump at study site or unable to have fresh HM delivered by designee at least once/day for 3 days within 3 hours of pumping AND located (in hospital or home) >30km from study sites (for courier services)

• Maximum Eligible Age: 33 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MOUNT SINAI HOSPITAL

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Rebecca Hoban, MD MPH

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rebecca Hoban, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

Gallipoli A, Unger S, El Shahed A, Fan CS, Signorile M, Wilson D, Hoban R. Outcomes after intranasal human milk therapy in preterm infants with intraventricular hemorrhage. J Perinatol. 2025 Feb;45(2):202-207. doi: 10.1038/s41372-024-02147-3. Epub 2024 Oct 9.

Reference Type: DERIVED

PMID: 39384614 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38688998 (View on PubMed)

Other Identifiers

1911

Identifier Type: -

Identifier Source: org_study_id