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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Safety Issues

Intervention / Treatment
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* Biological: autologous cord blood mononuclear cells
* Biological: normal saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACBMNC infusion group<br>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. | Biological: autologous cord blood mononuclear cells<br>* 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<br>|
| Placebo Comparator: control group<br>Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume per kg. | Biological: normal saline<br>* preterm neonates less than 32 weeks are assigned to receive normal saline within 24 hours after birth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | Number of Participants with Adverse Events, with abnormal vital signs and abnormal laboratory tests results | during 6 months after intervention | 
| success rate of cord blood collection | cord blood collection, cell available, infused cell number | during 6 months after intervention | 
| complications | frequency of complications such IVH, NEC, retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), LOS, and persistent pulmonary hypertension of newborn (PPHN) and anemia. | during 6 months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immnue cells number and frequency | immunomodulatory effect and the impacts on immune cells subsets | 36 weeks of postmenstrual age or the discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous cord blood mononuclear cells, monozygotic twins, very premature infants