Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)

The purpose of this study is to investigate the use of autologous umbilical cord blood (UCB) mononuclear cells to mitigate hypoxic neurologic injury among infants with high-risk congenital diaphragmatic hernia (CDH).

Study Overview

• Status: Terminated
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Biological: Autologous umbilical cord blood

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 minutes to 1 week (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of CDH between 20 and 36 weeks estimated gestational age (EGA)
• Only one of the following fetal criteria and one of the following postnatal criteria must be met for enrollment. Fetal criteria: an ultrasound (US)-obtained observed to expected lung to head ratio (o/e LHR) less than or equal to 35% or 2) a fetal magnetic resonance imaging (fMRI)- obtained observed to expected total fetal lung volume (o/e TFLV) less than or equal to 35%. Postnatal criteria: 1) Cord blood gas (CBG) with potenital hydrogen (pH) <7.0, 2) Arterial blood gas (ABG) with pH <7.2 on 2 gasses within the first 24 hours, 3) Preductal oxygen saturation (O2 sat) <90% x 2 total hours (not necessarily consecutive) within the first 24 hours, or 4) Oxygenation Index (OI) >20 x 2 total hours (not necessarily consecutive) within the first 24 hours.

Exclusion Criteria:

• Genetic/chromosomal abnormality: Trisomy 21, Trisomy 18, Trisomy 13 or other, significant genetic abnormality. Microdeletions or other mild genetic abnormalities are not considered exclusionary.
• Severe/major cardiac anomaly: coarctation of the aorta, combined atrial and ventricular septal defects, hypoplastic left heart syndrome, tetralogy of fallot, double outlet right ventricle, atrioventricular canal defects, or other hemodynamically significant defects.
• Moderate/severe neurologic / intracranial abnormality: Grade III or IV intraparenchymal hemorrhage, space occupying mass or lesion, or clinically significant traumatic lesion such as a subdural or epidural hemorrhage.
• Prematurity <30 weeks estimated gestational age (EGA): Birth at 29 6/7 weeks or before
• Participation in an alternative prenatal intervention study: Fetoscopic Endotracheal Occlusion (FETO)
• Unwillingness / inability to return for follow-up evaluation and assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous umbilical cord blood	Biological: Autologous umbilical cord blood; 6×10^6 mononuclear cells isolated from the patient's own umbilical cord blood per dose. 4 total doses administered intravenously over 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by vital sign monitoring (heart rate)		daily for 7 days following the initial infusion
Safety as assessed by vital sign monitoring (systolic blood pressure)		daily for 7 days following the initial infusion
Safety as assessed by vital sign monitoring (diastolic blood pressure)		daily for 7 days following the initial infusion
Safety as assessed by vital sign monitoring (temperature)		daily for 7 days following the initial infusion
Safety as assessed by pulmonary status (indicated by peak inspiratory pressure (PIP))		daily for 7 days following the initial infusion
Safety as assessed by pulmonary status (indicated by positive end expiratory pressure (PEEP))		daily for 7 days following the initial infusion
Safety as assessed by pulmonary status (indicated by respiratory rate (RR))		daily for 7 days following the initial infusion
Safety as assessed by pulmonary status (indicated by Fraction of inspired oxygen (FiO2))		daily for 7 days following the initial infusion
Safety as assessed by presence of new infiltrates or altered aeration upon chest radiography		daily for 7 days following the initial infusion
Safety as assessed by cardiovascular status (indicated by heart rate)		daily for 7 days following the initial infusion
Safety as assessed by cardiovascular status (indicated by systolic blood pressure)		daily for 7 days following the initial infusion
Safety as assessed by cardiovascular status (indicated by diastolic blood pressure)		daily for 7 days following the initial infusion
Safety as assessed by cardiovascular status (indicated by changes in cardiovascular pharmacologic support)		daily for 7 days following the initial infusion
Safety as assessed by infection status (indicated by body temperature)		daily for 7 days following the initial infusion
Safety as assessed by infection status (indicated by white blood cell count)		7 days following the initial infusion
Safety as assessed by infection status (indicated by physical signs of infection)		daily for 7 days following the initial infusion
Safety as assessed by liver function (indicated by Alanine aminotransferase (ALT) levels)		7 days following the initial infusion
Safety as assessed by liver function (indicated by aspartate aminotransferase (AST) levels		7 days following the initial infusion
Safety as assessed by liver function (indicated by bilirubin levels)		7 days following the initial infusion
Safety as assessed by liver function (indicated by albumin levels)		7 days following the initial infusion
Safety as assessed by blood urea nitrogen (BUN) levels		7 days following the initial infusion
Safety as assessed by creatinine levels		7 days following the initial infusion
Safety as assessed by carbon dioxide (CO2) levels		7 days following the initial infusion
Safety as assessed by glucose levels		7 days following the initial infusion
Safety as assessed by serum chloride levels		7 days following the initial infusion
Safety as assessed by serum potassium levels		7 days following the initial infusion
Safety as assessed by serum sodium levels		7 days following the initial infusion
Neurologic/neurodevelopmental status as assessed by intracranial abnormalities upon magnetic resonance imaging (MRI)		within 14 days of discharge (discharge occurs at about 2-4 months after birth)
Neurologic/neurodevelopmental status as assessed by receipt of neurologic pharmacologic medications		at the time of discharge (which is about 2-4 months after birth)
Neurologic/neurodevelopmental status as assessed by Bayley Scales of Infant and Toddler Development-III (BSID-III)	The Bayley-III is an individually-administered examination that assesses the current developmental functioning of infants and young children from birth to 42 months of age. The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15.	2 years after birth

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	2 years after birth
Length of stay in hospital	from birth to discharge or death, whichever occurs first (discharge occurs at about 2-4 months after birth)
Progression of pulmonary hypertension as assessed by echocardiography	within 24 hours of birth, prior to operative repair (occurs between day 2 & 14 of life), prior to discharge (usually 2-6 months), and after discharge (2wks-6 months following discharge)
Duration of extracorporeal membrane oxygenation (ECMO) support	days from ECMO initiation until decannulation (an average of 3 weeks)
Duration of ventilatory support	from initiation of ventilation until extubation (an average of 8 weeks)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Texas Medical Center Regenerative Medicine Consortium
• Investigators: Principal Investigator: Matthew T. Harting, MD, MS, The University of Texas Health Science Center, Houston

Publications and helpful links

Helpful Links

• The Comprehensive Center for CDH Care at Children's Memorial Hermann Hospital and The University of Texas Health Science Center in Houston (Texas Medical Center)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: April 27, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: CDH
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: HSC-MS-18-0148

Drug and device information, study documents

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