Clinical trial NCT03526588: Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)
Official title: Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Congenital Diaphragmatic Hernia
Keywords: CDH
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Texas Medical Center Regenerative Medicine Consortium
First posted: 2018-05-16
Enrollment: 3
Sex: ALL
Minimum age (years): 10
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Safety as assessed by vital sign monitoring (heart rate)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by vital sign monitoring (systolic blood pressure)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by vital sign monitoring (diastolic blood pressure)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by vital sign monitoring (temperature)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by pulmonary status (indicated by peak inspiratory pressure (PIP))
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by pulmonary status (indicated by positive end expiratory pressure (PEEP))
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by pulmonary status (indicated by respiratory rate (RR))
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by pulmonary status (indicated by Fraction of inspired oxygen (FiO2))
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by presence of new infiltrates or altered aeration upon chest radiography
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by cardiovascular status (indicated by heart rate)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by cardiovascular status (indicated by systolic blood pressure)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by cardiovascular status (indicated by diastolic blood pressure)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by cardiovascular status (indicated by changes in cardiovascular pharmacologic support)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by infection status (indicated by body temperature)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by infection status (indicated by white blood cell count)
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by infection status (indicated by physical signs of infection)
timeFrame: daily for 7 days following the initial infusion
measure: Safety as assessed by liver function (indicated by Alanine aminotransferase (ALT) levels)
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by liver function (indicated by aspartate aminotransferase (AST) levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by liver function (indicated by bilirubin levels)
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by liver function (indicated by albumin levels)
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by blood urea nitrogen (BUN) levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by creatinine levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by carbon dioxide (CO2) levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by glucose levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by serum chloride levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by serum potassium levels
timeFrame: 7 days following the initial infusion
measure: Safety as assessed by serum sodium levels
timeFrame: 7 days following the initial infusion
measure: Neurologic/neurodevelopmental status as assessed by intracranial abnormalities upon magnetic resonance imaging (MRI)
timeFrame: within 14 days of discharge (discharge occurs at about 2-4 months after birth)
measure: Neurologic/neurodevelopmental status as assessed by receipt of neurologic pharmacologic medications
timeFrame: at the time of discharge (which is about 2-4 months after birth)
measure: Neurologic/neurodevelopmental status as assessed by Bayley Scales of Infant and Toddler Development-III (BSID-III)
timeFrame: 2 years after birth
Secondary outcomes:
measure: Mortality
timeFrame: 2 years after birth
measure: Length of stay in hospital
timeFrame: from birth to discharge or death, whichever occurs first (discharge occurs at about 2-4 months after birth)
measure: Progression of pulmonary hypertension as assessed by echocardiography
timeFrame: 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)
measure: Duration of extracorporeal membrane oxygenation (ECMO) support
timeFrame: days from ECMO initiation until decannulation (an average of 3 weeks)
measure: Duration of ventilatory support
timeFrame: from initiation of ventilation until extubation (an average of 8 weeks)
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Matthew T. Harting, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: