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NCT Number: NCT04255147

Cellular Therapy for Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a common and chronic lung disease that occurs in preterm infants following ventilator and oxygen therapy and is associated with long-term health consequences. Preclinical research shows that mesenchymal stromal cells (MSCs) can modify a number of pathophysiological processes that are central to the progression of BPD and thus present as a promising new treatment option. The main purpose of this Phase I study is to evaluate the safety of human umbilical cord tissue-derived MSCs in extremely preterm infants at risk of developing BPD.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

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

Age range

7 day–28 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The Ottawa Hospital - General Campus, Gloucester, Ontario, Canada

Loading trial locations.

About this study

Complications of extreme preterm birth are the primary cause of mortality in children under the age of five. Bronchopulmonary dysplasia (BPD), the chronic lung disease that follows ventilator and oxygen therapy for acute respiratory failure, is the most common complication of extreme prematurity and contributes to life-long respiratory and neurological impairment. Currently, there is no effective treatment for BPD. The multi-factorial nature of BPD makes it challenging for traditional pharmacological therapies targeting a single pathway to have a major impact on outcome. Mesenchymal stromal cells (MSCs) may provide a promising new treatment avenue due to their pleiotropic effects that may prevent neonatal lung injury while promoting lung (and other organ) growth. A systematic review and meta-analysis of all preclinical studies testing MSCs in neonatal lung injury models provides strong evidence for the lung protective effect of MSCs. Additionally, studies in a large preclinical model of extreme prematurity and chronic lung injury suggest feasibility, safety and short-term hemodynamic benefit of intravenously delivered human umbilical cord tissue-derived MSCs (uc-MSC).

The aim of this study is to establish the safety, maximum feasible dose and feasibility of intravenously delivered allogeneic uc-MSCs in preterm infants at risk of developing BPD. This will be a Phase 1, open-label, single center, dose-escalating trial using a 3+3+3 design.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

A participant needs to meet all inclusion criteria between day of life 7-28 to be eligible:

Inclusion criteria

  • Admission to The Ottawa Hospital (TOH) NICU - General Campus or Sunnybrook Health Sciences Centre NICU
  • Gestational age at birth < 28 weeks
  • Intubated on mechanical ventilation
  • Fraction of inspired oxygen ≥ 30%
  • Parents or substitute decision make must provide written informed consent

Exclusion criteria

  • Severe congenital anomaly by antenatal ultrasound and physical examination
  • Ongoing shock and severe sepsis (confirmed by positive blood or cerebrospinal fluid culture) as per attending physician
  • Severe pulmonary hemorrhage
  • Active pneumothorax (with chest tube in-situ)
  • Hemodynamically significant PDA
  • Participants with caregiver unable to speak English or French
  • Patient i moribund, not expected to survive
  • Planned to be extubated in the 24 hours after uc-MSC administration

Treatment and study plan

Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells

Biological

Cryopreserved allogeneic umbilical cord tissue-derived mesenchymal stromal cells are thawed and administered intravenously.

Primary outcomes

  1. Occurrence and rate of dose limiting toxicity

    Time frame: Up to 1 week following uc-MSC injection

    Dose limiting toxicity consists of the following events:

    • Death occurring within 24 hours of injection;
    • Pulmonary embolism defined as acute increase in right ventricular afterload (identified by serial targeted neonatal echocardiography) and signs of acute increased dead space ventilation (respiratory distress, increased PaCO2, increased minute ventilation) occurring within 24 hours of injection;
    • Hypersensitivity / anaphylactic to uc-MSCs defined as any severe systemic inflammatory response syndrome with negative blood culture not consistent with the overall clinical course of the infant occurring within 72 hours of injection;
    • Any other serious adverse event not expected in this patient population for which there is no alternative explanation but the administration of uc-MSCs, occurring within 1 week of injection.

Secondary outcomes

  1. Rate of Death

    Time frame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

    Rate of death until discharge or 40 weeks corrected gestational age, whichever comes first

  2. Occurrence of Other Severe Complications of Prematurity

    Time frame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

    • Blood culture-proven sepsis
    • Patent ductus arteriosus (treated medically or surgically)
    • Necrotizing enterocolitis
    • Isolated intestinal perforation
    • Retinopathy of prematurity requiring treatment
    • Severe intraventricular hemorrhage (≥ grade 3)
    • Cystic periventricular leukomalacia

  3. FiO2 and Oxygen Index

    Time frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

    Measures of gas exchange

  4. Need for Ventilatory Support

    Time frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

    • Time to extubation
    • Duration of mechanical ventilation
    • Duration of non-invasive positive pressure respiratory support
    • Duration of supplemental oxygen

  5. Need for Postnatal Steroids

    Time frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

    This is a yes/no measure

  6. Incidence and Severity of BPD

    Time frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

    Measured as mild, moderate, or severe

  7. Rate of Survival Without (moderate or severe) BPD

    Time frame: From enrollment until 36 weeks corrected gestational age

    Measured according to the physiological definition of BPD (BPD at 36 weeks corrected age)

  8. Changes in Pulmonary Hemodynamics

    Time frame: At enrollment, 48 hours following uc-MSC injection, 28 days of life, and 36 weeks corrected gestational age

    Targeted neonatal echocardiography to assess pulmonary hypertension using validated parameters

  9. Biological Measure of Clinical Improvement

    Time frame: 72-96 hours following uc-MSC injection

    Markers of inflammation will be assessed in patient serum samples

  10. Biological Measure of Lung Improvement

    Time frame: 72-96 hours following uc-MSC injection

    Biomarkers of lung improvement will be assessed in patient tracheal aspirate samples

  11. Feasibility: Cell Administration

    Time frame: Day of life 7-28

    Successful recruitment and administration of cells to nine patients in 18 months

  12. Feasibility: Recruitment Efficiency

    Time frame: Day of life 7-28

    • Proportion of potentially eligible patients that are successfully screened
    • Proportion of participants successfully screened who do not enroll (reason for failure to enroll will be recorded)

  13. Feasibility: Recruitment Timing

    Time frame: Day of life 7-28

    • Median time from screening to enrollment
    • Median time from screening to cell administration

  14. Feasibility: Participant Retainment

    Time frame: From enrollment until follow-up at 18-30 months-of-age

    • Proportion of patients that do not complete cell infusion
    • Proportion of patients enrolled that do not undergo scheduled follow-up

  15. Bayley Scale of Infant and Toddler Development

    Time frame: 18-30 months-of-age

    Assessment of cognitive, language, and motor development

  16. Long-term Safety Follow-Up

    Time frame: Ten years following follow-up visit

    Participant's overall health will be assessed through a questionnaire administered over the phone, once a year for 10 years

  17. Animated Information Video

    Time frame: Day of life 7-28

    Characterize parental views of an animated MSC information video through brief semi-structured interviews

Sponsors and collaborators

Lead sponsor

Ottawa Hospital Research Institute

Other

Collaborators

  • Canadian Institutes of Health Research (CIHR)
  • Ontario Institute for Regenerative Medicine
  • Stem Cell Network

Registry information

Official study title

Helping Underdeveloped Lungs With Cells (HULC): Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - Phase 1 Study

Important dates

Study start
2022
Primary completion
2023
Study completion
2033
First posted
Feb 5, 2020
Registry last updated
Jul 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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