Mesenchymal Stromal Cell Therapy to Prevent Bronchopulmonary Dysplasia in Extreme Preterm Infants (HULC-2)

July 8, 2025 updated by: Ottawa Hospital Research Institute

Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - A Phase 2 Multi-Centre Double Blind Randomized Controlled Trial

This clinical trial aims to evaluate the safety and efficacy of mesenchymal stromal cell (MSC) therapy in extreme preterm infants to prevent bronchopulmonary dysplasia, the main respiratory complication of preterm birth.

Study participants will receive either multiple intravenous doses (total of 3 doses) of MSC derived from human donor umbilical cord tissue (intervention group) or no uc-MSC injection (control group) to confirm the safety of IV MSC in extreme preterm infants and evaluate the potential benefit of MSC therapy on their respiratory health as well as on other complications related to preterm birth.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Include Background...

Study Type

Interventional

Enrollment (Estimated)

168

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Bernard Thébaud, MD, PhD
  • Phone Number: 73905 613-737-8899
  • Email: bthebaud@toh.ca

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T5H 3V9
        • Royal Alexandra Hospital/Stollery Children's Hospital
        • Contact:
        • Principal Investigator:
          • Georg Schmölzer, MD, PhD
    • Ontario
      • Hamilton, Ontario, Canada, L8Z 3Z5
        • McMaster Children's Hospital
        • Principal Investigator:
          • Amit Mukerji
        • Contact:
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital
      • Toronto, Ontario, Canada, M5G 1X5
      • Toronto, Ontario, Canada, M4Y 3M5
        • Sunnybrook Health Sciences Ctr
        • Contact:
        • Principal Investigator:
          • Maher Shahroor, MD, RCPSC
        • Sub-Investigator:
          • Elizabeth Asztalos, MD, MSc, FRCPC
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine
        • Contact:
        • Principal Investigator:
          • Anne-Monique Nuyt
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill Montreal Children's Hospital
        • Contact:
        • Principal Investigator:
          • Marc Beltempo, MD, M.Sc., FRCPC
      • Québec City, Quebec, Canada, G1V 0B4
        • Université Laval
        • Contact:
        • Principal Investigator:
          • Mireille Guillot

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Gestational age (GA) less than 28+0 weeks
  • Post-natal age between 4 and 14 days of life

  • Invasive ventilation with oxygen requirement:

    • On mechanical ventilation: intubated patient with any of the following ventilation modes: conventional, HFO or Jet ventilation:
    • With requirement of FiO2: FiO2 >= 30% and for at least 12 hours over 24 hours (i.e. flowsheets, FiO2 histogram)

Exclusion Criteria:

  1. Congenital anomaly:

    • Genetic and chromosomal syndromes (e.g., Trisomy 13, Trisomy 18, Trisomy 21): either patient with high suspicion (antenatal findings, clinical features) or documented syndrome by genetic testing.
    • Major congenital anomalies including cardiac (i.e., congenital heart defects, NB. PDA is not considered an exclusion criterion), neurological (e.g., holoprosencephaly, anencephaly), gastrointestinal (e.g., gastroschisis, omphalocele), pulmonary (e.g., congenital diaphragmatic hernia) anomalies.
    • Inborn errors of metabolism.

  2. Hemodynamic instability (shock):

    • Hemodynamic instability with impaired end-organ perfusion (metabolic acidosis with increased lactate and/or decreased urine output).
    • Requirements for fluid bolus, inotrope or vasopressor medication

  3. Severe sepsis:

    • Signs of hemodynamic instability and requiring at least one fluid bolus.
    • And a positive blood or cerebrospinal fluid culture.
  4. Pneumothorax: Pneumothorax with a chest tube in place

  5. Severe pulmonary hemorrhage:

    • Active pulmonary hemorrhage (i.e., frank blood coming from the endotracheal tube.
    • And at least one of the following criteria: a)hemodynamic instability. b) blood product transfusion (packed red blood cells, platelets, fresh frozen plasma)
  6. Extubation: If Extubation planned within the next 24 hours (post first uc-MSC administration/sham procedure).

  7. Patient is not expected to survive:

    • Redirection of care.
    • Patient is moribund

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group will receive multiple IV doses of UC-MSCs
  • Dose: each dose consists of 10 million cells/kilograms of bodyweight.
  • Administration protocol: weekly (7 days ± 1 day) IV dose of UC-MSCs for 3 weeks (Total of 3 doses)
  • Route of administration: IV infusion on peripheral intravenous catheter. The UC-MSC solution will be infused using a syringe pump over 15 minutes, and after the UCMSC infusion, an additional volume of normal saline will be infused over 15 minutes.
Biological: Human Allogenic Umbilical Cord Mesenchymal Stromal Cells
IV administration of uc-MSC every 7 days ± 1 day for 3 weeks. Randomized double blinded
Other Names:
  • UC-MSC
  • Mesenchymal Stromal Cells
  • Umbilical Cord Mesenchymal Stromal Cells
Sham Comparator: Control group
Participants allocated in the control group will receive a sham procedure weekly for 3 weeks. A syringe of normal saline brought to bedside, but it will not be administered. The physician and bedside nurse will perform the sham procedure behind a screen (they will mimic IV catheter insertion and cell product injection)
Other: Sham procedure control
Sham procedure (mimic IV catheter insertion adn cell product infusion behing a screen). Repeated weekly for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of mechanical ventilation-free days accounting for mortality
Time Frame: 120 days
The study primary outcome is the number of mechanical ventilation-free days accounting for mortality. Mechanical ventilation is defined by artificial ventilation using an endotracheal tube. For study purpose, this outcome will be measured at 120 days after randomization. To account for mortality, any death within 120 days post randomization will be counted as "0" mechanical ventilation-free day (worse outcome).
120 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of uc-MSCs on the date of extubation for participants.
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
This respiratory outcome will be measured to determine if uc-MSCs have an effect on the date of extubation for participants
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
Effects of uc-MSCs on the rate of survival without moderate or severe BPD at 36 weeks corrected age.
Time Frame: BPD severity will be assessed for each participant at 36 weeks of corrected age
This will assess if uc-MSCs impact survival with moderate or severe Bronchopulmonary dysplasia.
BPD severity will be assessed for each participant at 36 weeks of corrected age
Effects of uc-MSCs on the Number of Participants receiving open-label dexamethasone for severe chronic lung disease
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
This will help us determine if the intervention reduces use of dexamethasone for the treatment of severe chronic lung disease.
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
Effects of uc-MSCs on the duration of respiratory support.
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months

Since ventilation damages underdeveloped lungs, determining the duration of ventilation is important to monitor as an outcome of uc-MSCs.

We will collect the total number of days on mechanical ventilation, non-invasive ventilation, and oxygen therapy during the NICU hospitalization for each participant
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
Effects of uc-MSCs on the levels of respiratory support at 36 weeks CA, 40 weeks CA and at hospital discharge.
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months

The different levels of intensity of ventilation will help us determine if uc-MSCs reduce ventilation days.

The respiratory support being used are the following (Room air being the least intensive and best for participant health outcome.):

mechanical ventilation vs. Continuous Positive Airway pressure/High Flow Nasal Canula, vs. Low Flow Nasal Canula vs. room air
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
Effects of uc-MSCs on the occurrence of pulmonary hypertension related to severe BPD
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months

This will help us determine the therapeutic properties of UC-MSCs in reducing the occurrence of pulmonary hypertension related to severe BPD.

Participants will be screened by echocardiography for pulmonary hypertension at 36 weeks of corrected age. Medication for chronic pulmonary hypertension will be collected.
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months
Neurodevelopment and health outcomes at 24 months corrected age (Bayleys)
Time Frame: Assessment will be scheduled at 24 months corrected age.
The neurodevelopmental assessment will be scheduled at 24 months CA with a window of +/- 6 months (i.e., between 18 to 30 months CA). Participants will be evaluated in the Neonatal Follow-Up clinic for high-risk infants. An assessment of general health and growth will be performed, and the most recent audiology and ophthalmology results will be recorded. The Bayley Scales of Infant Develpment-4th edition will be performed by a qualified professional to further evaluate the neurodevelopment of the participant.
Assessment will be scheduled at 24 months corrected age.
Evaluation of safety of IV administration of UC-MSCs: Dose Limiting toxicity
Time Frame: 24-hours post uc-MSC injection

Dose-limiting toxicity, defined as one of the following events, occurring within 24-hour post UC-MSC injection:

  • Death
  • Anaphylaxis
  • Increase need for respiratory support define by increase FiO2 >30% from baseline and/or increase in mean airway pressure > 5 cmH2O from baseline
  • Medications to support hemodynamic status (including management of cardiac arrest) including fluid boluses, inotropes, or vasopressors
  • Any SAE not expected in this patient population for which there is no alternative explanation but the IV administration of UC-MSCs and occurring within 1 week after UC-MSCs injection.
24-hours post uc-MSC injection
Evaluation of safety of IV administration of UC-MSCs: potential adverse event
Time Frame: within 1 week post uc-MSC injection
Any Serious Adverse Event (SAE) not expected in this patient population for which there is no alternative explanation but the IV administration of UC-MSCs and occurring within 1 week after UC-MSCs injection.
within 1 week post uc-MSC injection
Long-term participant safety follow-up
Time Frame: From enrollment until participant is 10 years of age.
We plan to have annual parental interviews via telephone until the participant is 10 years old. This is to assess the respiratory status and any new diagnoses of study participants.
From enrollment until participant is 10 years of age.
Complications of prematurity (assessed at time of hospital discharge)
Time Frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months

The complications of prematurity assessed are the following:

  • BPD.
  • Patent Ductus Arteriosus requiring medical, surgical or device closure.
  • Intra-ventricular hemorrhage ≥ grade 3 according to Papille's classification.
  • Periventricular leukomalacia.
  • Necrotizing enterocolitis ≥ stage 2 according to Bell's classification.
  • Retinopathy of prematurity requiring treatment
  • Late-onset sepsis
From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Hospital Research Institute

Collaborators

Canadian Institutes of Health Research (CIHR)
Stem Cell Network

Investigators

  • Principal Investigator: Bernard Thébaud, MD, PhD, Ottawa Hospital Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2025

Primary Completion (Estimated)

September 30, 2028

Study Completion (Estimated)

September 30, 2038

Study Registration Dates

First Submitted

May 26, 2025

First Submitted That Met QC Criteria

July 8, 2025

First Posted (Actual)

July 10, 2025

Study Record Updates

Last Update Posted (Actual)

July 10, 2025

Last Update Submitted That Met QC Criteria

July 8, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HULC-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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