Safety and Feasibility Study of Umbilical Cord Blood Cells for Infants With Hypoplastic Left Heart Syndrome

Phase 1

Terminated

• Conditions: Hypoplastic Left Heart Syndrome
• Interventions: Biological: Autologous Umbilical Cord Blood

• Registration Number: NCT01445041
• Lead Sponsor: Michael Cotten

Brief Summary

Further study details as provided by Duke University:

Purpose: To evaluate the feasibility and safety of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS).

Study Rationale and Hypotheses: The major goal of this study is to determine whether infusion of autologous UCB cells in neonates with hypoplastic left heart syndrome is feasible and safe. The rationale for the study and for the potential benefit of UCB is based upon the following hypotheses:

1. Infants with HLHS have significant neural injury evidenced from both prenatal and early antenatal brain MRI findings and infusion of UCB cells may lessen neural injury. Although the exact mechanism is unknown, UCB cell infusion may ameliorate neural injury via paracrine and anti-inflammatory effects that enhance post injury repair and may promote endogenous functional compensation of other cortical areas resulting in significant clinical improvements.

2. UCB cells may also enhance cardiac function, minimize scar formation, and reverse detrimental remodeling after cardiac injury.

Detailed Description

The purpose of this pilot study is to evaluate the safety and feasibility of infusions of autologous (the patient's own)umbilical cord blood cells in neonates with hypoplastic left heart syndrome. This is a prospective, randomized Phase I trial designed to assess the safety and feasibility of autologous UCB reinfusion in neonates with Hypoplastic Left Heart Syndrome (HLHS). Neonates who are identified prenatally as having a cardiac lesion consistent with HLHS will be referred to Duke Cardiology for further evaluation. If they meet inclusion criteria, UCB will be collected at the time of delivery and processed (red blood cell- and volume-reduced) for reinfusion. All enrolled infants will receive a dose of fresh UCB cells pre-operatively and ½ of the enrolled infants will be randomly selected to receive a second dose of frozen and thawed UCB cells after stage 1 palliation (5-35 days post-operatively) and a third dose of frozen and thawed UCB cells 2 to 4 weeks after the 2nd infusion. Neurodevelopmental outcome measures will be assessed at 1 month after discharge, at 4-6 months old and 12 months. The results of MRI's and echocardiograms that are obtained per clinical routine will be analyzed and described in study reports.

Study Timeline

• Study Start: 2011-09-01
• Study First Submitted: 2011-09-15
• Study First Submitted QC: 2011-09-29
• Study First Posted: 2011-10-03
• Primary Completion: 2016-04-15
• Study Completion: 2016-04-15
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Infants > 35 weeks gestational age.
• Diagnosis: Hypoplastic Left Heart Syndrome.
• Autologous umbilical cord blood available with a minimum total nucleated cell dose of 1 x 10e7 cells/kg.
• Parental Consent.

Exclusion Criteria

• Chromosomal anomalies identified before the time of infusion.

• Chromosomal anomalies or congenital anomalies that would prohibit clinicians from initiating surgical repair of the congenital heart defect.

• Infant is determined by clinical staff to be non-viable and will not receive aggressive care. (No member on the study team will be involved in determining the viability of the neonate.)

• Autologous umbilical cord blood unit has any of the following:

  • Total nuclear cell count < 1 x 10e7.
  • Positive maternal infectious serology (except CMV).
  • Evidence of infectious contamination of the cord blood unit.
  • Evidence of genetic disease.

• Unable to obtain parental consent.

• Mother < 18 years old.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Three infusions of UCB	Autologous Umbilical Cord Blood	(autologous red blood cell and volume reduced cord blood cells)
Single infusion of UCB	Autologous Umbilical Cord Blood	(autologous red blood cell and volume reduced cord blood cells)

Primary Outcome Measures

Name	Time	Method
Adverse event rates occurring in the pilot study population. The investigators will compare infusion outcomes of infants infused with frozen cells and infants infused with non-frozen cells.	During Infusions (First 2 months of life)

Secondary Outcome Measures

Name	Time	Method
Feasibility and preliminary efficacy	1 year	Feasibility: volume of cord blood, cell viability, time to prepare/infuse fresh cells and frozen-thawed cells.; Preliminary efficacy: neurodevelopmental outcomes at 9 - 12 months, cardiac function as assessed clinically.

Trial Locations

Locations (1)

Duke University; 🇺🇸 Durham, North Carolina, United States