Efficacy Evaluation of UCB-MNCs in the Treatment of Refractory Neonatal Diseases

Efficacy Evaluation of Umbilical Cord Blood-derived Mononuclear Cells in the Treatment of Refractory Neonatal Diseases

Hypoxic-ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), short bowel syndrome (SBS) are refractory in clinical treatment. Thus, how to better prevent such diseases is currently a key research topic in the international field. The use of cord blood-derived mononuclear cells may promote to save lives and improve patient outcomes.

Study Overview

• Status: Recruiting
• Conditions: Bronchopulmonary Dysplasia; Hypoxic-Ischemic Encephalopathy; Short Bowel Syndrome
• Intervention / Treatment: Biological: Mononuclear cells; Device: Mild hypothermia therapy; Device: Breathing support technique; Procedure: Total parenteral nutrition

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yujie Han, MD; Phone Number: +86 187 5414 6336; Email: 410358192@qq.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Qilu Children's Hospital of Shandong University
      • Contact: Xiaoying Li; Email: lxy_jn@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For children with hypoxic-ischemic encephalopathy (HIE): meet the diagnostic criteria for HIE.

For children with bronchopulmonary dysplasia (BPD): 1) preterm infants with definite gestational age of 25-30 weeks; 2) birth weight 401-1249 g; 3) the risk of BPD was assessed to be greater than 60%. The scoring was based on the BPD high risk scoring system established by the NCHD Neonatal Cooperative Network; 4)parents read the subject's instructions, agreed to the treatment and signed the informed consent.

For children with short bowel syndrome (SBS): 1) postoperative short bowel syndrome caused by neonatal necrotizing enterocolitis and other causes (developmental malformations of the digestive tract: intestinal atresia, anal atresia, intestinal stenosis, etc.); 2) parents read the subject's instructions, agreed to the treatment and signed the informed consent.

Exclusion Criteria:

• For children with HIE: unable or unwilling to provide informed consent or unable to comply with trial requirements.

For children with BPD: 1) with severe anemia, severe intracranial hemorrhage, pulmonary hemorrhage, congenital respiratory malformations (posterior nostril atresia, tracheoesophageal fistula, cleft palate, etc.), complicated congenital heart disease, diaphragmatic hernia, shock, other serious comorbidities or complications (congenital inherited metabolic diseases, endocrine diseases, severe congenital malformations and other diseases that affect lung development); 2) unable or unwilling to provide informed consent or unable to comply with trial requirements.

For children with SBS: unable or unwilling to provide informed consent or unable to comply with trial requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group for children with HIE; Intravenous infusion of UCB-MNCs is given within 24 hours of being identified as a high-risk patient	Biological: Mononuclear cells; UCB-MNCs are obtained from umbilical cord blood by density gradient centrifugation; Device: Mild hypothermia therapy; Mild hypothermia therapy via hypothermia therapy apparatus
Active Comparator: Control group for children with HIE; Mild hypothermia therapy is given for 72 hours to maintain anal temperature between 33.5°C and 34°C	Device: Mild hypothermia therapy; Mild hypothermia therapy via hypothermia therapy apparatus
Experimental: Experimental group for children with BPD; Intravenous infusion of UCB-MNCs is given within 24 hours of being identified as a high-risk patient	Biological: Mononuclear cells; UCB-MNCs are obtained from umbilical cord blood by density gradient centrifugation; Device: Breathing support technique; Breathing support via ventilator
Active Comparator: Control group for children with BPD; Clinical routine treatment	Device: Breathing support technique; Breathing support via ventilator
Experimental: Experimental group for children with SBS; Intravenous infusion of UCB-MNCs	Biological: Mononuclear cells; UCB-MNCs are obtained from umbilical cord blood by density gradient centrifugation; Procedure: Total parenteral nutrition; Liquid nutrition injected directly into the bloodstream
Active Comparator: Control group for children with SBS; Clinical routine treatment	Procedure: Total parenteral nutrition; Liquid nutrition injected directly into the bloodstream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse reactions	Monitor oxygen, heart rate, temperature, rash, infection, etc	Within 12 hours after UCB-MNCs infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complications	Children with BPD: The incidence of various complications such as pneumothorax, necrotizing enterocolitis (NEC), intraventricular hemorrhage (grade 3 and above), persistent pulmonary hypertension (PPHN), retinopathy of prematurity (ROP)	a year
Imaging test results	Children with HIE: Brain diffusion tensor imaging (DTI) and 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT)	2 weeks and 6 months after UCB-MNCs infusion
Electroencephalography (EEG) results	Children with HIE: The frequency of seizures will be measured via EEG. Seizures appear on EEG as a sudden and transient rise in the lower and/or upper borders of amplitude	7 days UCB-MNCs infusion
Ventilator supporting time	Ventilator supporting time and oxygen demand will be recorded as important indications for clinical prognosis for children with HIE or BPD	1 month after UCB-MNCs infusion
Change of Gross Motor Performance Measure (GMPM)	GMPM is a standardized measurement tool for assessing quality of movement for children with HIE. Higher value means better motor quality	1, 3, 6 months after UCB-MNCs infusion
Change of Gross Motor Function Measure (GMFM)	GMFM is a standardized measurement tool for assessing motor function for children with HIE. It consists of lying & rolling, sitting, crawling & kneeling, standing, etc. Higher value means better gross motor function	1, 3, 6 months after UCB-MNCs infusion
Biomarker of HIE	pNF-H, marker of central nervous system axonal damage	7 days after UCB-MNCs infusion
Biomarker of BPD	AGER, marker of lung epithelial cell damage	7 days after UCB-MNCs infusion
Inflammatory indicators concentrations	Serum IL-6, IL-8, TNF concentrations will be measured via ELISA for children with HIE, BPD or SBS	7 days after UCB-MNCs infusion

Collaborators and Investigators

• Sponsor: Shandong Qilu Stem Cells Engineering Co., Ltd.
• Collaborators: Qilu Children's Hospital of Shandong University
• Investigators: Principal Investigator: Xiaoying Li, MD, Qilu Children's Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 19, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Postoperative Complications; Gastrointestinal Diseases; Intestinal Diseases; Signs and Symptoms, Respiratory; Malabsorption Syndromes; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Hypoxia; Hypoxia, Brain; Brain Ischemia; Brain Diseases; Bronchopulmonary Dysplasia; Hypoxia-Ischemia, Brain; Infant, Newborn, Diseases; Short Bowel Syndrome
• Other Study ID Numbers: MNCs-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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