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

NCT ID: NCT04255147

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-17
• Study Completion Date: 2033-11-06

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.

Detailed Description

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.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells

Intervention Type: BIOLOGICAL

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

Interventions

Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 7 Days
• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ontario Institute of Regenerative Medicine (OIRM)

UNKNOWN

Sponsor Role: collaborator

Stem Cell Network

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bernard Thébaud, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

The Ottawa Hospital - General Campus

Gloucester, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

HULC-1

Identifier Type: -

Identifier Source: org_study_id