Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Stem Cell Network | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Include Background...
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group will receive multiple IV doses of UC-MSCs | Experimental |
|
|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human Allogenic Umbilical Cord Mesenchymal Stromal Cells | Biological | IV administration of uc-MSC every 7 days ± 1 day for 3 weeks. Randomized double blinded |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Effects of uc-MSCs on the date of extubation for participants. | 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 |
Not provided
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:
Exclusion Criteria:
Congenital anomaly:
Hemodynamic instability (shock):
Severe sepsis:
Pneumothorax: Pneumothorax with a chest tube in place
Severe pulmonary hemorrhage:
Extubation: If Extubation planned within the next 24 hours (post first uc-MSC administration/sham procedure).
Patient is not expected to survive:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bernard Thébaud, MD, PhD | Contact | 613-737-8899 | 73905 | bthebaud@toh.ca |
| Chantal Horth | Contact | chorth@cheo.on.ca |
| Name | Affiliation | Role |
|---|---|---|
| Bernard Thébaud, MD, PhD | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Alexandra Hospital/Stollery Children's Hospital | Edmonton | Alberta | T5H 3V9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42409407 | Derived | Renesme L, Ferretti E, Horth C, Grimwood R, Da Sylva L, Olson V, Cyr-Depauw C, Freund D, Rudiger M, Mobius MA, Hodgins S, Khan S, Courtman D, Fergusson DA, Thebaud B. Helping Underdeveloped Lungs with Cells (HULC-2): mesenchymal stromal cells in extreme preterm infants at risk of developing bronchopulmonary dysplasia - a study protocol of a phase 2 multicentre double blind randomised controlled trial in Canada. BMJ Open. 2026 Jul 6;16(7):e112385. doi: 10.1136/bmjopen-2025-112385. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Intervention group:
Participants allocated in the intervention group will receive multidose of UC-MSCs as follow:
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)
Not provided
Not provided
Parents of the participants.
|
| Sham procedure control | Other | Sham procedure (mimic IV catheter insertion adn cell product infusion behing a screen). Repeated weekly for 3 weeks |
|
| Effects of uc-MSCs on the rate of survival without moderate or severe BPD at 36 weeks 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 | 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. | 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. | 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 | 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) | 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 | Dose-limiting toxicity, defined as one of the following events, occurring within 24-hour post UC-MSC injection:
| 24-hours post uc-MSC injection |
| Evaluation of safety of IV administration of UC-MSCs: potential adverse event | 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 | 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) | The complications of prematurity assessed are the following:
| 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 |
| McMaster Children's Hospital | Hamilton | Ontario | L8Z 3Z5 | Canada |
|
| The Ottawa Hospital | Ottawa | Ontario | K1H 8L6 | Canada |
| Sunnybrook Health Sciences Ctr | Toronto | Ontario | M4Y 3M5 | Canada |
|
| Mount Sinai Hospital | Toronto | Ontario | M5G 1X5 | Canada |
|
| CHU Sainte-Justine | Montreal | Quebec | H3T 1C5 | Canada |
|
| McGill Montreal Children's Hospital | Montreal | Quebec | H4A 3J1 | Canada |
|
| Université Laval | Québec | Quebec | G1V 0B4 | Canada |
|
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
Not provided
Not provided