## Protocol Section
### Identification Module
**NCT ID:** NCT06427642

**Brief Title:** Efficacy Evaluation of UCB-MNCs in the Treatment of Refractory Neonatal Diseases

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

#### Organization Study ID Info
**ID:** MNCs-2024
#### Organization
**Class:** INDUSTRY
**Full Name:** Shandong Qilu Stem Cells Engineering Co., Ltd.
### Status Module
#### Completion Date
**Date:** 2025-04-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-19

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-05-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-04-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-19
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Qilu Children's Hospital of Shandong University

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Shandong Qilu Stem Cells Engineering Co., Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Hypoxic-Ischemic Encephalopathy

- Bronchopulmonary Dysplasia

- Short Bowel Syndrome

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Intravenous infusion of UCB-MNCs is given within 24 hours of being identified as a high-risk patient

**Intervention Names:**

- Biological: Mononuclear cells

- Device: Mild hypothermia therapy

**Label:** Experimental group for children with HIE

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Mild hypothermia therapy is given for 72 hours to maintain anal temperature between 33.5°C and 34°C

**Intervention Names:**

- Device: Mild hypothermia therapy

**Label:** Control group for children with HIE

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** Intravenous infusion of UCB-MNCs is given within 24 hours of being identified as a high-risk patient

**Intervention Names:**

- Biological: Mononuclear cells

- Device: Breathing support technique

**Label:** Experimental group for children with BPD

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Clinical routine treatment

**Intervention Names:**

- Device: Breathing support technique

**Label:** Control group for children with BPD

**Type:** ACTIVE_COMPARATOR

#### Arm Group 5

**Description:** Intravenous infusion of UCB-MNCs

**Intervention Names:**

- Biological: Mononuclear cells

- Procedure: Total parenteral nutrition

**Label:** Experimental group for children with SBS

**Type:** EXPERIMENTAL

#### Arm Group 6

**Description:** Clinical routine treatment

**Intervention Names:**

- Procedure: Total parenteral nutrition

**Label:** Control group for children with SBS

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Experimental group for children with BPD

- Experimental group for children with HIE

- Experimental group for children with SBS

**Description:** UCB-MNCs are obtained from umbilical cord blood by density gradient centrifugation

**Name:** Mononuclear cells

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Control group for children with HIE

- Experimental group for children with HIE

**Description:** Mild hypothermia therapy via hypothermia therapy apparatus

**Name:** Mild hypothermia therapy

**Type:** DEVICE

#### Intervention 3

**Arm Group Labels:**

- Control group for children with BPD

- Experimental group for children with BPD

**Description:** Breathing support via ventilator

**Name:** Breathing support technique

**Type:** DEVICE

#### Intervention 4

**Arm Group Labels:**

- Control group for children with SBS

- Experimental group for children with SBS

**Description:** Liquid nutrition injected directly into the bloodstream

**Name:** Total parenteral nutrition

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Monitor oxygen, heart rate, temperature, rash, infection, etc

**Measure:** Incidence of adverse reactions

**Time Frame:** Within 12 hours after UCB-MNCs infusion

#### Secondary Outcomes

**Description:** 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)

**Measure:** Incidence of complications

**Time Frame:** a year

**Description:** Children with HIE: Brain diffusion tensor imaging (DTI) and 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT)

**Measure:** Imaging test results

**Time Frame:** 2 weeks and 6 months after UCB-MNCs infusion

**Description:** 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

**Measure:** Electroencephalography (EEG) results

**Time Frame:** 7 days UCB-MNCs infusion

**Description:** Ventilator supporting time and oxygen demand will be recorded as important indications for clinical prognosis for children with HIE or BPD

**Measure:** Ventilator supporting time

**Time Frame:** 1 month after UCB-MNCs infusion

**Description:** GMPM is a standardized measurement tool for assessing quality of movement for children with HIE. Higher value means better motor quality

**Measure:** Change of Gross Motor Performance Measure (GMPM)

**Time Frame:** 1, 3, 6 months after UCB-MNCs infusion

**Description:** 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

**Measure:** Change of Gross Motor Function Measure (GMFM)

**Time Frame:** 1, 3, 6 months after UCB-MNCs infusion

**Description:** pNF-H, marker of central nervous system axonal damage

**Measure:** Biomarker of HIE

**Time Frame:** 7 days after UCB-MNCs infusion

**Description:** AGER, marker of lung epithelial cell damage

**Measure:** Biomarker of BPD

**Time Frame:** 7 days after UCB-MNCs infusion

**Description:** Serum IL-6, IL-8, TNF concentrations will be measured via ELISA for children with HIE, BPD or SBS

**Measure:** Inflammatory indicators concentrations

**Time Frame:** 7 days after UCB-MNCs infusion

### Eligibility Module

**Eligibility Criteria:** 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.

**Maximum Age:** 28 Days

**Minimum Age:** 1 Day

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 410358192@qq.com

**Name:** Yujie Han, MD

**Phone:** +86 187 5414 6336

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Jinan

**Contacts:**

***Contact 1:***

- **Email:** lxy_jn@sina.com

- **Name:** Xiaoying Li

- **Role:** CONTACT

**Country:** China

**Facility:** Qilu Children's Hospital of Shandong University

**State:** Shandong

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** Qilu Children's Hospital of Shandong University

**Name:** Xiaoying Li, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000055397

- Term: Ventilator-Induced Lung Injury

- ID: D000055370

- Term: Lung Injury

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000007235

- Term: Infant, Premature, Diseases

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000002534

- Term: Hypoxia, Brain

- ID: D000000860

- Term: Hypoxia

- ID: D000012818

- Term: Signs and Symptoms, Respiratory

- ID: D000008286

- Term: Malabsorption Syndromes

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000011183

- Term: Postoperative Complications

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10543

- Name: Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M4185

- Name: Hypoxia

- Relevance: LOW

- As Found: Unknown

- ID: M5794

- Name: Brain Ischemia

- Relevance: HIGH

- As Found: Ischemic Encephalopathy

- ID: M15586

- Name: Short Bowel Syndrome

- Relevance: HIGH

- As Found: Short Bowel Syndrome

- ID: M5273

- Name: Bronchopulmonary Dysplasia

- Relevance: HIGH

- As Found: Bronchopulmonary Dysplasia

- ID: M10276

- Name: Infant, Newborn, Diseases

- Relevance: HIGH

- As Found: Neonatal Disease

- ID: M5204

- Name: Brain Diseases

- Relevance: HIGH

- As Found: Encephalopathy

- ID: M22660

- Name: Hypoxia-Ischemia, Brain

- Relevance: HIGH

- As Found: Hypoxic Ischemic Encephalopathy

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M28143

- Name: Lung Injury

- Relevance: LOW

- As Found: Unknown

- ID: M28152

- Name: Ventilator-Induced Lung Injury

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25869

- Name: Premature Birth

- Relevance: LOW

- As Found: Unknown

- ID: M10279

- Name: Infant, Premature, Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5783

- Name: Hypoxia, Brain

- Relevance: LOW

- As Found: Unknown

- ID: M15623

- Name: Signs and Symptoms, Respiratory

- Relevance: LOW

- As Found: Unknown

- ID: M11278

- Name: Malabsorption Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14065

- Name: Postoperative Complications

- Relevance: LOW

- As Found: Unknown

- ID: T874

- Name: Bronchopulmonary Dysplasia

- Relevance: HIGH

- As Found: Bronchopulmonary Dysplasia

- ID: T5206

- Name: Short Bowel Syndrome

- Relevance: HIGH

- As Found: Short Bowel Syndrome

### Condition Browse Module - Meshes

- ID: D000012778

- Term: Short Bowel Syndrome

- ID: D000001997

- Term: Bronchopulmonary Dysplasia

- ID: D000001927

- Term: Brain Diseases

- ID: D000002545

- Term: Brain Ischemia

- ID: D000020925

- Term: Hypoxia-Ischemia, Brain

- ID: D000007232

- Term: Infant, Newborn, Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M4854

- Name: Benzocaine

- Relevance: LOW

- As Found: Unknown

- ID: T433

- Name: Tannic Acid

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
