Autologous Cord Blood Mononuclear Cell in Preventing Complications of Monozygotic Twins in Very Premature Infants

Autologous Cord Blood Mononuclear Cell in Preventing Complications of Monozygotic Twins in Very Premature Infants

Autologous Cord Blood Mononuclear Cell in Preventing Complications of Monozygotic Twins in Very Premature Infants: a Placebo-controlled Randomized Single-center Trial

This is a the first-in-human randomized, placebo-controlled, double-blinded phase I clinical trial assessing the feasibility, safety and initial effect of intravenous ACBMNC infusion in very preterm monozygotic twins

Study design and settings: This study will be a randomized, placebo-controlled, double-blinded, single-center trial. A total of 8 pairs of monozygotic twins fulfilling the eligibility criteria will be enrolled. Subsequently, one baby of each twin will be randomly divided into the ACBMNC infusion group or control (placebo) group. Trial treatment methods: Soon after the preterm infant was deliveried, written consent was signed by the parents, and autologous cord blood infusion was applied to the baby in addition to routine treatment. Those assigned to the ACBMNC group received an infusion of ACBMNC . Those in control group received an infusion of a placebo solution. Informed consent before birth is signed. Preterm infants in the ACBMNC infusion group will have their umbilical cord blood collected after birth, and then their umbilical cord blood will be separated through Guangdong Province umbilical cord blood Bank to obtain mesenchymal stem cells. Within 24h after birth, ACBMNC group received an infusion of mesenchymal stem cells timely, while control (placebo) group received an infusion of a placebo solution which is normal saline with the same volume. Cell dose for all patients was targeted at2-10×107 cells per kilogram.

In this prospective, randomized controlled double-blind clinical trial, 6-8 pairs of monozygotic twins less than 32 weeks are enrolled, in which one of each twin is randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (2-10×107cells/kg) or placebo ( normal saline) within 24 hours after birth.

Once the enrollment was confirmed, the research physician contacted the research nurse. They were informed with the assignment and prepared the processed cord blood MNC or normal saline. After preparation, infusion bag was covered with shading bag and infused by light-blocking infusion tube, so that the nurses who conducted the infusion and all physicians who treated the baby were not aware of the treatment assignment. We used the code name of ACBMNC number 1 or number 2 to name the infusion fluid in the computerized physician order entry. The staff who collected and analyzed the patients' data and who followed up the patients were also blinded with the assignment. The research nurse and physician that knew the allocation of treatment did not make decisions in baby's clinical care. The parents or guardians were also not aware of the assignment. Therefore, this study was double-blinded.

Those assigned to the ACBMNC group will receive intravenous autologous cord blood mononuclear cells infusion within 24 h after process. Cell dose for all patients was 2-10×107 cells per kilogram.

Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume per kg.

preterm neonates less than 32 weeks are assigned to receive intravenous autologous cord blood mononuclear cells infusion (2-10×107cells/kg) within 24 hours after birth

preterm neonates less than 32 weeks are assigned to receive normal saline within 24 hours after birth

Number of Participants with Adverse Events, with abnormal vital signs and abnormal laboratory tests results

frequency of complications such IVH, NEC, retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), LOS, and persistent pulmonary hypertension of newborn (PPHN) and anemia.

Duration of mechanical ventilation, oxygen therapy and hospitalization at 36 weeks of postmenstrual age or the discharge

the frequence of glucocorticoid, pulmonary surfactant, blood products and re-intubation at 36 weeks of postmenstrual age or the discharge

Inclusion criteria born at study hospitals; monozygotic twins (confirmed by ultrasonographic diagnosis before birth and confirm again with obstetricians during and after delivery, as monochorionic diamniotic twins and monochorionic monoamniotic Twins twins were both monozygotic twins, therefore they will be both eligible); gestational age (GA) <32 weeks (GA was calculated based on the date of the last menstrual period of the mother and an ultrasonographic screening performed during the first trimester of pregnancy); enrolled within the first 24 postnatal hours; free of severe perinatal asphyxia (defined as an Apgar score of 0-3 for more than 5 minutes, a cord blood gas pH <7.00, or both); free of severe congenital anomalies or genetic syndromes; free of maternal sepsis24,25; Written informed consent is obtained from the parents or guardians of the infants; Either of the twins has available umbilical cord blood (UCB) , and the cell number was no more than 10×107 cells per kilogram, but should not be less than 2×107 cells per kilogram. Exclusion criteria (1) they exhibit severe congenital abnormalities (detected via prenatal ultrasound); (2) expected to die within the first 24 hours; (3) diagnosed with severe twin-to-twin transfusion syndrome confirmed by prenatal ultrasonography24.