Clinical trial NCT03774537: Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia
Official title: Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Premature Infants Ａt High Risk For Bronchopulmonary
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Bronchopulmonary Dysplasia
Keywords: high risk； Bronchopulmonary Dysplasia；hUC-MSCs
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2018-12-13
Enrollment: 20
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is an open-label, single-center, dose escalation study to evaluate of safety and efficacy of human umbilical cord -derived mesenchymal stem cells (hUC-MSCs) in premature infants at high risk for Bronchopulmonary Dysplasia（BPD）

Detailed description: BPD is a chronic lung disease that occur in premature infants receiving prolonged oxygen pulmonary and ventilator therapy. It remains a main complication of extreme prematurity and currently lacks efficient treatment.The mortality rate of one year after birth is still high and the quality of life is not optimistic.

hUC-MSCs are widely used in clinic due to their low immunogenicity and convenient to get. Many animal study had shown that hUC-MSCs had therapeutic effects on a variety of animal models of lung disease.Furthermore,there are a large number of clinical trials of MSCs applied to various system diseases and the safety was verified.So, the main purpose of this study is to evaluate the safety and efficacy of hUC-MSCs in participants at high risk for BPD

Eligibility criteria: Inclusion Criteria:

1. An infant whose postnatal age is 3 to 14 days, inclusive (for treatment between 5 and 14 days after birth)
2. Gestational age is between 23 and 28 weeks (23 weeks ≤ gestational age (GA) \< 28 weeks)
3. Birth weight is between 500g and 1000g, inclusive
4. Being intubated and receiving mechanical ventilation within 5-14 days after birth, with a fraction of inspired oxygen (FiO2) of 0.25 or greater at Screening
5. Written consent form signed by a legal representative or a parent.

Exclusion Criteria:

1. Although mechanical ventilation or oxygen is required in participants, there are no signs of dyspnea or BPD-related changes in lung imaging, such as central apnea or diaphragm paralysis.
2. The participants who have complex congenital heart disease.
3. The participants who have severe pulmonary hypertension(cardiac ultrasound confirmed) at the time of assessment.
4. The participants who have severe respiratory tract malformation: pierre-robin syndrome, tracheobronchomalacia, vascular ring syndrome, congenital tracheal stenosis, tracheo-esophageal fistula, pulmonary emphysema, pulmonary sequestration, congenital pulmonary dysplasia, congenital pulmonary cyst, congenital spasm, etc.
5. The participants who have severe chromosome anomalies :Edward syndrome, Patau syndrome, Down syndrome, etc) or severe congenital malformation (Hydrocephalus, Encephalocele, etc).
6. The participants who have severe congenital infection(Herpes, Toxoplasmosis, Rubella, Syphilis, AIDS, etc).
7. The participants who have severe sepsis or shock.
8. The participants who is going to have surgery 72 hours before/after this study drug administration.
9. The participants who have surfactant administration within 24 hours before this study drug administration.
10. The participants who have severe intracranial hemorrhage ≥ grade 3 or 4.
11. The participants who have active pulmonary hemorrhage or active air leak syndrome at the time of assessment.
12. The participants who have the history of other clinical studies as a participant.
13. The participants who is considered inappropriate by the investigators.

Primary outcomes:
measure: Number of participants with adverse reactions related to infusion after treatment
timeFrame: 24 hours after administration
Secondary outcomes:
measure: The incidence and severity of BPD defined by the National Institutes of Child Health and Human Development (NICHD) workshop.
timeFrame: at the corrected gestational age of 36 weeks
measure: Changes of high-resolution chest CT in participants
timeFrame: within 2 years after administration
measure: Changes of temperature in participants
timeFrame: 3 days after administration
measure: Changes of blood pressure in participants
timeFrame: 3 days after administration
measure: Changes of respiratory rate in participants
timeFrame: 3 days after administration
measure: Changes of oxygen saturation in participants
timeFrame: 3 days after administration
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Zhou Fu
role: STUDY_CHAIR
References:
citation: Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966-972.e6. doi: 10.1016/j.jpeds.2013.12.011. Epub 2014 Feb 6.
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citation: Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, Kourembanas S. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012 Apr-Jun;2(2):170-81. doi: 10.4103/2045-8932.97603.
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