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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Ontario Institute for Regenerative Medicine | OTHER |
| Stem Cell Network | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mesenchymal Stromal Cell Therapy | Experimental | Patients are enrolled into one of three escalating dose panels based on the time of enrolment. The first three patients will receive 1 million cells/kg of body weight, the next three patients will receive 3 million cells/kg of body weight, and the final three patients will receive 10 million cells/kg of body weight. Progression through the escalating dose panels is subject to review by an independent Data Safety Monitoring Committee. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells | Biological | Cryopreserved allogeneic umbilical cord tissue-derived mesenchymal stromal cells are thawed and administered intravenously. |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence and rate of dose limiting toxicity | Dose limiting toxicity consists of the following events:
| Up to 1 week following uc-MSC injection |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Death | Rate of death until discharge or 40 weeks corrected gestational age, whichever comes first | From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first) |
| Occurrence of Other Severe Complications of Prematurity |
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A participant needs to meet all inclusion criteria between day of life 7-28 to be eligible:
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bernard Thébaud, MD, PhD | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Ottawa Hospital - General Campus | Gloucester | Ontario | K1T 8L6 | Canada | ||
| Sunnybrook Health Sciences Centre |
Due to the small sample size, the sharing of individual data has privacy and confidentiality implications.
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| 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 |
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| From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first) |
| FiO2 and Oxygen Index | Measures of gas exchange | From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first) |
| Need for Ventilatory Support |
| From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first) |
| Need for Postnatal Steroids | This is a yes/no measure | From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first) |
| Incidence and Severity of BPD | Measured as mild, moderate, or severe | From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first) |
| Rate of Survival Without (moderate or severe) BPD | Measured according to the physiological definition of BPD (BPD at 36 weeks corrected age) | From enrollment until 36 weeks corrected gestational age |
| Changes in Pulmonary Hemodynamics | Targeted neonatal echocardiography to assess pulmonary hypertension using validated parameters | At enrollment, 48 hours following uc-MSC injection, 28 days of life, and 36 weeks corrected gestational age |
| Biological Measure of Clinical Improvement | Markers of inflammation will be assessed in patient serum samples | 72-96 hours following uc-MSC injection |
| Biological Measure of Lung Improvement | Biomarkers of lung improvement will be assessed in patient tracheal aspirate samples | 72-96 hours following uc-MSC injection |
| Feasibility: Cell Administration | Successful recruitment and administration of cells to nine patients in 18 months | Day of life 7-28 |
| Feasibility: Recruitment Efficiency |
| Day of life 7-28 |
| Feasibility: Recruitment Timing |
| Day of life 7-28 |
| Feasibility: Participant Retainment |
| From enrollment until follow-up at 18-30 months-of-age |
| Bayley Scale of Infant and Toddler Development | Assessment of cognitive, language, and motor development | 18-30 months-of-age |
| Long-term Safety Follow-Up | Participant's overall health will be assessed through a questionnaire administered over the phone, once a year for 10 years | Ten years following follow-up visit |
| Animated Information Video | Characterize parental views of an animated MSC information video through brief semi-structured interviews | Day of life 7-28 |
| Toronto |
| Ontario |
| M4N 3M5 |
| Canada |
| 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 |