Mesenchymal Stromal Cell Therapy to Prevent Bronchopulmonary Dysplasia in Extreme Preterm Infants

NCT07058025 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: HULC-2
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Bronchopulmonary Dysplasia (BPD); ELGAN (22-28SA)

Keywords

Phase II clinical trial; Mesenchymal stromal cell; Cell therapy; Preterm infant; Bronchopulmonary Dysplasia; Extremely low gestational age neonates

Outcome Measures

Primary Outcomes (1)

• Number of mechanical ventilation-free days accounting for mortality

  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 Outcomes (11)

• Effects of uc-MSCs 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.

  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

  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.

  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.

  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

Study Arms (2)

Intervention group will receive multiple IV doses of UC-MSCs

EXPERIMENTAL

* 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

Control group

SHAM COMPARATOR

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

Interventions

Human Allogenic Umbilical Cord Mesenchymal Stromal Cells BIOLOGICAL

IV administration of uc-MSC every 7 days ± 1 day for 3 weeks. Randomized double blinded

Also known as: UC-MSC, Umbilical Cord Mesenchymal Stromal Cells, Mesenchymal Stromal Cells

Intervention group will receive multiple IV doses of UC-MSCs

Sham procedure control OTHER

Sham procedure (mimic IV catheter insertion adn cell product infusion behing a screen). Repeated weekly for 3 weeks

Control group

Eligibility Criteria

• Age: 4 Days - 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• Inborn errors of metabolism.
• 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
• Severe sepsis:
• Signs of hemodynamic instability and requiring at least one fluid bolus.
• And a positive blood or cerebrospinal fluid culture.
• Pneumothorax: Pneumothorax with a chest tube in place
• 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)
• Extubation: If Extubation planned within the next 24 hours (post first uc-MSC administration/sham procedure).
• Patient is not expected to survive:

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Stem Cell Network: collaborator

Study Sites (8)

Royal Alexandra Hospital/Stollery Children's Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8Z 3Z5, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Ctr

Toronto, Ontario, M4Y 3M5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

McGill Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Université Laval

Québec, Quebec, G1V 0B4, Canada

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Bernard Thébaud, MD, PhD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernard Thébaud, MD, PhD

CONTACT

613-737-8899; bthebaud@toh.ca

Chantal Horth

CONTACT

chorth@cheo.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parents of the participants.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention group: Participants allocated in the intervention group will receive multidose of UC-MSCs as follow: * Dose: each dose consists of 10x106 cells/kilograms of bodyweight. * Administration protocol: weekly 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 using a syringe pump over 15 minutes. 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)

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: July 10, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2038
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8)