Effect of Autologous Cord Blood-mononuclear Cells Infusion on Immune Microenvironment in Infants Born Very Preterm in NICU

Effect of Autologous Cord Blood-mononuclear Cells Infusion on Immune Microenvironment in Infants Born Very Preterm in NICU: a Randomized Controlled Trial -The Premature Autologous Cord-blood Immunomodulatory Study (PAIRS)

Multi-omics (analysis of peripheral blood immune cells subset, peripheral blood MNCs transcriptome, soluble inflammatory cytokine profile in blood and airway secretion, lung and gut microbiota, and the interaction) analysis was used to profile immune alternation of infants with intravenous ACBMNC infusion in very preterm monozygotic twins

Study Overview

• Status: Completed
• Conditions: Immunomodulation Effect
• Intervention / Treatment: Biological: normal saline; Biological: autologous cord blood mononuclear cells

Detailed Description

This was a randomized, placebo-controlled, double-blinded trial involving eight pairs of VPMTs who were admitted to NICU to receive respiratory support right after birth. The infants were assigned (1:1) to receiving at least 2×107 ACB-MNCs/kg or normal saline, intravenously, within 24-h post-enrollment within each pair. Multi-omics (analysis of peripheral blood immune cells subset, peripheral blood MNCs transcriptome, soluble inflammatory cytokine profile in blood and airway secretion, lung and gut microbiota, and the interaction) analysis was used to profile immune alternation of infants with ACB-MNCs infusion, along with paired controls. Feasibility, safety and clinical outcomes improvement of the ACB-MNCs infusion in both short and long term were also assessed.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 511400
      • Jie Yang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

1. born at study hospitals;
2. 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);
3. 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);
4. enrolled within the first 24 postnatal hours;
5. 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);
6. free of severe congenital anomalies or genetic syndromes;
7. free of maternal sepsis24,25;
8. Written informed consent is obtained from the parents or guardians of the infants;
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACBMNC infusion group; 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; 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
Placebo Comparator: control group; 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; preterm neonates less than 32 weeks are assigned to receive normal saline within 24 hours after birth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
immunomodulation effect	analysis of peripheral blood immune cells subset, peripheral blood MNCs transcriptome, soluble inflammatory cytokine profile in blood and airway secretion, lung and gut microbiota, and the interaction	during 7 days 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation, oxygen therapy and hospitalization	Duration of mechanical ventilation, oxygen therapy and hospitalization at 36 weeks of postmenstrual age or the discharge	36 weeks of postmenstrual age or the discharge
the frequence of glucocorticoid, pulmonary surfactant, blood products and re-intubation	the frequence of glucocorticoid, pulmonary surfactant, blood products and re-intubation at 36 weeks of postmenstrual age or the discharge	36 weeks of postmenstrual age or the discharge

Collaborators and Investigators

• Sponsor: Guangdong Women and Children Hospital
• Investigators: Study Chair: Jie Yang, Guangdong Women and Children Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2021
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: October 9, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 24, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: autologous cord blood mononuclear cells; monozygotic twins; very premature infants
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: Guangdong M CH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: public
• IPD Sharing Time Frame: All time
• IPD Sharing Access Criteria: all
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No