Clinical trial NCT03558334: Human Mesenchymal Stem Cells For Bronchopulmonary Dysplasia
Official title: Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Moderate and Severe Bronchopulmonary Dysplasia in Premature Infants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Bronchopulmonary Dysplasia
Keywords: Bronchopulmonary Dysplasia
human umbilical cord -derived mesenchymal stem cells
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2018-06-15
Enrollment: 12
Sex: ALL
Minimum age (years): 28
Standard ages: CHILD
ADULT
OLDER_ADULT
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 for moderate and severe 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 with moderate and severe BPD.

Eligibility criteria: Inclusion Criteria:

1. The participants meet the diagnostic criteria for moderate and severe BPD established by the National Institutes of Child Health and Human Development (NICHD) workshop.
2. The participants have abnormal respiratory manifestations.
3. 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: 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 heart rate 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
measure: Growth velocity (Z-score) in participants
timeFrame: within 2 years 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.
citation: Hayes D Jr, Meadows JT Jr, Murphy BS, Feola DJ, Shook LA, Ballard HO. Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care. Prim Care Respir J. 2011 Jun;20(2):128-33. doi: 10.4104/pcrj.2011.00002.
citation: Ahn SY, Chang YS, Kim JH, Sung SI, Park WS. Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia. J Pediatr. 2017 Jun;185:49-54.e2. doi: 10.1016/j.jpeds.2017.02.061. Epub 2017 Mar 21.
citation: Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17.
citation: Laube M, Stolzing A, Thome UH, Fabian C. Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth. Int J Biochem Cell Biol. 2016 May;74:18-32. doi: 10.1016/j.biocel.2016.02.023. Epub 2016 Feb 27.
citation: Pierro M, Ionescu L, Montemurro T, Vadivel A, Weissmann G, Oudit G, Emery D, Bodiga S, Eaton F, Peault B, Mosca F, Lazzari L, Thebaud B. Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia. Thorax. 2013 May;68(5):475-84. doi: 10.1136/thoraxjnl-2012-202323. Epub 2012 Dec 4.
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.