Cellular Therapy for Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia
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| ClinicalTrials.gov Identifier: NCT04255147 |
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Recruitment Status :
Recruiting
First Posted : February 5, 2020
Last Update Posted : April 3, 2023
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Sponsor:
Ottawa Hospital Research Institute
Collaborators:
Canadian Institutes of Health Research (CIHR)
Ontario Institute of Regenerative Medicine (OIRM)
Stem Cell Network
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Bronchopulmonary Dysplasia | Biological: Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 9 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | Helping Underdeveloped Lungs With Cells (HULC): Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - Phase 1 Study |
| Actual Study Start Date : | October 17, 2022 |
| Estimated Primary Completion Date : | September 30, 2023 |
| Estimated Study Completion Date : | December 2035 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Mesenchymal Stromal Cell Therapy
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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Biological: Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells
Cryopreserved allogeneic umbilical cord tissue-derived mesenchymal stromal cells are thawed and administered intravenously. |
Primary Outcome Measures :
- 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 Outcome Measures :
- 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
- 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
- FiO2 and Oxygen Index [ Time Frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first) ]Measures of gas exchange
- 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
- 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
- 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
- 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)
- 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
- Biological Measure of Clinical Improvement [ Time Frame: 72-96 hours following uc-MSC injection ]Markers of inflammation will be assessed in patient serum samples
- 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
- Feasibility: Cell Administration [ Time Frame: Day of life 7-21 ]Successful recruitment and administration of cells to nine patients in 18 months
- Feasibility: Recruitment Efficiency [ Time Frame: Day of life 7-21 ]
- 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)
- Feasibility: Recruitment Timing [ Time Frame: Day of life 7-21 ]
- Median time from screening to enrollment
- Median time from screening to cell administration
- Feasibility: Participant Retainment [ Time Frame: From enrollment until follow-up at 18-24 months-of-age ]
- Proportion of patients that do not complete cell infusion
- Proportion of patients enrolled that do not undergo scheduled follow-up
- Bayley Scale of Infant and Toddler Development [ Time Frame: 18-24 months-of-age ]Assessment of cognitive, language, and motor development
- 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
- Animated Information Video [ Time Frame: Day of life 7-21 ]Characterize parental views of an animated MSC information video through brief semi-structured interviews
Information from the National Library of Medicine
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| Ages Eligible for Study: | 7 Days to 21 Days (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Admission to The Ottawa Hospital General Campus Neonatal Intensive Care Unit
- Gestational age at birth < 28 weeks
- Day of life 7-21
- Intubated on mechanical ventilation
- Fraction of inspired oxygen ≥ 35%
- Parents or surrogates must provide written informed consent
Exclusion Criteria:
- Severe congenital anomaly by antenatal ultrasound and physical examination
- Ongoing shock and severe sepsis
- Active pulmonary hemorrhage
- Active pneumothorax (with chest tube in-situ)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04255147
Contacts
| Contact: Study Coordinator | 613-737-7600 ext 6041 | chorth@cheo.on.ca |
Locations
| Canada, Ontario | |
| The Ottawa Hospital - General Campus | Recruiting |
| Gloucester, Ontario, Canada, K1T 8L6 | |
| Contact: Chantal Horth 613-737-7600 ext 6041 chorth@cheo.on.ca | |
| Contact: Rebecca Grimwood 613-737-7600 ext 2794 rgrimwood@cheo.on.ca | |
| Principal Investigator: Bernard Thebaud, MD | |
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Institutes of Health Research (CIHR)
Ontario Institute of Regenerative Medicine (OIRM)
Stem Cell Network
Investigators
| Principal Investigator: | Bernard Thébaud, MD, PhD | Ottawa Hospital Research Institute |
| Responsible Party: | Ottawa Hospital Research Institute |
| ClinicalTrials.gov Identifier: | NCT04255147 |
| Other Study ID Numbers: |
HULC-1 |
| First Posted: | February 5, 2020 Key Record Dates |
| Last Update Posted: | April 3, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Due to the small sample size, the sharing of individual data has privacy and confidentiality implications. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by Ottawa Hospital Research Institute:
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Phase I clinical trial Stem cells Mesenchymal stromal cell |
Bronchopulmonary Dysplasia Preterm birth Cell therapy |
Additional relevant MeSH terms:
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Bronchopulmonary Dysplasia Hyperplasia Pathologic Processes Ventilator-Induced Lung Injury Lung Injury |
Lung Diseases Respiratory Tract Diseases Infant, Premature, Diseases Infant, Newborn, Diseases |