Intraventricular HemorrhageNCT04225286
Intranasal Human Milk for Intraventricular Hemorrhage
A study testing Human breast milk in people with Intraventricular Hemorrhage, run by The Hospital for Sick Children at 2 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 33 weeks
- Conditions the study is for
- Intraventricular Hemorrhage
- What is being tested?
- Human breast milk
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesCanada
- Study dates
- 11 Mar 2020to Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 33 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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"
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: Intranasal Human Milk as Stem Cell Therapy in Preterm Infants With Intraventricular Hemorrhage
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
- Being tested
- Human breast milk
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human breast milkOther
Intranasal human breast milk
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Human breast milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Cerebral Palsy, Gross motor delay (in the absence of CP), Fine motor delay, Vision impairment (blindness or wears glasses), Hearing impairment (aided / cochlear implant), Cognitive delay, Speech and language delay
Measured: 2 years
Interference of IHM administration with routine clinical care measured using post-intervention staff survey
Measured: 1 year
Number of participants with any grade IVH unable to be recruited within 10 days of birth
Measured: 1 year
Number of eligible patients unable to receive intranasal HM administration within 3 hours of HM collection
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start11 Mar 2020
- Primary completion1 Dec 2021
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intraventricular HemorrhageStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL
- Responsible party
- Principal investigator, Rebecca Hoban, MD MPH, The Hospital for Sick Children
- Investigators
- Rebecca Hoban, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225286
- Sponsor's protocol ID
- 1911
- Status last verified
- May 2022
- First submitted
- 20 Dec 2019
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39384614Hoban 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 38688998
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Human Milk as Stem Cell Therapy in Preterm Infants With Intraventricular Hemorrhage
- ClinicalTrials.gov ID
- NCT04225286
- Acronym / sponsor ID
- 1911
- Conditions
- Intraventricular Hemorrhage
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 37 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL
- Study start
- 11 Mar 2020 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- Dec 2023 (estimated)
- First posted
- 13 Jan 2020 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intranasal human breast milk | Experimental | Other: Human breast milkHuman 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 |
Who may qualify
- Ages
- Up to 33 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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"
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Human breast milkIntranasal human breast milk | Other | Intranasal human breast milk |
Primary outcome
Number of participants with treatment-related adverse events as described in the protocol
Time frame: 1 year
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.
4 secondary outcomes
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.
Time frame: 2 years
Interference of IHM administration with routine clinical care measured using post-intervention staff survey
Time frame: 1 year
Number of participants with any grade IVH unable to be recruited within 10 days of birth
Time frame: 1 year
Number of eligible patients unable to receive intranasal HM administration within 3 hours of HM collection
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Derived from this study: PubMed 39384614Gallipoli 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.
- Derived from this study: 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.
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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. This study is not recruiting at the moment.
Rebecca Hoban, MD principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Human breast milk in people with Intraventricular Hemorrhage, run by The Hospital for Sick Children at 2 sites in Canada.
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 1 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as described in the protocol (time frame: 1 year). 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 NCT04225286, which also lists 2 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 4 May 2022.