The Ottawa Hospital Research Institute, in collaboration with multiple Canadian research centers and supported by the Canadian Institutes of Health Research and the Stem Cell Network, will soon begin a Phase 2 multi-center randomized controlled trial testing mesenchymal stromal cell (MSC) therapy for the prevention of bronchopulmonary dysplasia (BPD) in extreme preterm infants.
The study, known as HULC-2, is scheduled to launch in October 2025 and will be conducted at several major hospitals across Canada.
Bronchopulmonary dysplasia is a serious and common complication in extremely premature infants—born before 28 weeks of gestation—where the lungs do not develop properly and are often further damaged by mechanical ventilation. BPD can lead to long-term respiratory problems and neurodevelopmental issues. Current treatment options are limited and mainly supportive, highlighting the need for innovative therapies. In this trial, researchers will investigate whether intravenous infusions of human umbilical cord-derived MSCs can safely reduce the incidence and severity of BPD in this high-risk population. Participants (n=168) will be randomized into two groups:
- Intervention Group: Will receive three weekly intravenous doses of UC-MSCs (10 million cells per kilogram of body weight per dose), infused over 15 minutes via peripheral IV catheter, followed by a saline flush.
- Control Group: Will undergo a sham procedure mimicking the infusion process (including bringing a saline syringe to the bedside and simulated administration behind a screen), but will not receive any actual IV infusion.
Both clinicians and families will be blinded to treatment allocation. The primary objective is to determine if MSC therapy increases the number of days infants are free from mechanical ventilation by 120 days after randomization, with deaths within this period counted as zero ventilation-free days. Key secondary outcomes include:
- Date of extubation
- Rate of survival without moderate or severe BPD at 36 weeks corrected age
- Need for open-label dexamethasone for chronic lung disease
- Total duration and types of respiratory support required
- Occurrence of pulmonary hypertension related to severe BPD
- Neurodevelopmental and general health outcomes at 24 months corrected age (Bayley Scales assessment)
- Assessment of safety, including any dose-limiting toxicities and serious adverse events associated with UC-MSC infusion
- Long-term follow-up for respiratory health and new diagnoses until age 10
- Rates of other complications of prematurity (e.g., intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis)
The investigators report that this trial is designed with a quadruple-blind structure (blinding participants, care providers, investigators, and outcome assessors) to minimize bias. All infants eligible for the study must be less than 28 weeks’ gestational age, between 4 and 14 days old, and require invasive ventilation with significant oxygen support.
The study is notable for using allogeneic umbilical cord-derived MSCs, a cell population thought to have immunomodulatory and tissue-protective properties, with emerging evidence suggesting potential benefits for lung repair in preterm infants. Preclinical and early-phase clinical studies, according to the researchers, have indicated that MSCs may reduce lung inflammation and fibrosis. However, definitive evidence from large-scale randomized trials remains lacking, making this investigation a significant step in the field. The trial’s primary completion is expected in September 2028, with final long-term follow-up data collection projected through 2038.
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