Intranasal Human Milk for Intraventricular Hemorrhage

NCT04225286 | Unknown DMC

• 1 other identifier: 1911
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as described in the protocol

  Increased respiratory support settings or increase in Fio2 by more than 10% for more than 1 hour after the intervention, need for PPV/bagging immediately (within 5 minutes) of administration, or need for escalation of respiratory modality (ie NC to CPAP or NIV to intubation) in the hour after administration.

  1 year

Secondary Outcomes (4)

• The number of participants with IVH related long-term adverse neurodevelopmental outcomes compared with a cohort of HM-fed historical controls with IVH from 30 months prior to the intervention cohort.

  2 years

• Interference of IHM administration with routine clinical care measured using post-intervention staff survey

  1 year

• Number of participants with any grade IVH unable to be recruited within 10 days of birth

  1 year

• Number of eligible patients unable to receive intranasal HM administration within 3 hours of HM collection

  1 year

Other Outcomes (2)

• Number of stem cells in maternal milk provided by lactating parents of preterm infants

  1 year

• Number of stem cells measured in CSF of treated infants who have lumbar punctures for clinical indications.

  1 year

Study Arms (1)

Intranasal human breast milk

EXPERIMENTAL

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

Other: Human breast milk

Interventions

Human breast milk OTHER

Intranasal human breast milk

Intranasal human breast milk

Eligibility Criteria

• Age: Up to 33 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. 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"

You may not qualify if:

• Disorders associated with neurodevelopmental delays or impairment (i.e. Trisomy 21)
• Moribund/critically ill infant or known lethal diagnosis with plans by medical team to redirect care
• Choanal atresia or anomalies that would not allow intranasal treatment
• Surgical condition (e.g. esophageal atresia) for which team feels intranasal HM is contraindicated
• Enrolled in other intervention trials in which primary target is neurodevelopmental outcome
• Parent with lactation contraindication(s) (i.e. HIV) or parent who declines lactation initiation
• 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)

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• MOUNT SINAI HOSPITAL: collaborator

Study Sites (2)

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  PMID: 39384614 DERIVED

• 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.

  PMID: 38688998 DERIVED

MeSH Terms

Interventions

Milk, Human

Intervention Hierarchy (Ancestors)

Milk; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Dairy Products; Food; Food and Beverages

Study Officials

• Rebecca Hoban, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 13, 2020
• Study Start: March 11, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2023
• Last Updated: May 4, 2022

Record last verified: 2022-05

Locations

CA (2)