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

Autologous Cord Blood Cells for Patients With HLHS: Phase I Study of Feasibility and Safety

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.

Study Overview

• Status: Terminated
• Conditions: Hypoplastic Left Heart Syndrome
• Intervention / Treatment: Biological: Autologous Umbilical Cord Blood; Biological: Autologous Umbilical Cord Blood

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 days (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single infusion of UCB; (autologous red blood cell and volume reduced cord blood cells)	Biological: Autologous Umbilical Cord Blood; Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 1 infusion of their own volume reduced cord blood cells. The dose for each infusion is 5x10e7 cells/kg.; Biological: Autologous Umbilical Cord Blood; Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 3 infusions of their own volume reduced cord blood cells. The first infusion will be a fresh, volume-reduced infusion and the subsequent infusions will be thawed and washed infusions. The dose for each infusion is 5x10e7 cells/kg.
Experimental: Three infusions of UCB; (autologous red blood cell and volume reduced cord blood cells)	Biological: Autologous Umbilical Cord Blood; Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 1 infusion of their own volume reduced cord blood cells. The dose for each infusion is 5x10e7 cells/kg.; Biological: Autologous Umbilical Cord Blood; Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 3 infusions of their own volume reduced cord blood cells. The first infusion will be a fresh, volume-reduced infusion and the subsequent infusions will be thawed and washed infusions. The dose for each infusion is 5x10e7 cells/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Feasibility and preliminary efficacy	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.	1 year

Collaborators and Investigators

• Sponsor: Michael Cotten
• Investigators: Principal Investigator: Charles M Cotten, MD MHS, Duke University

Publications and helpful links

General Publications

• Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.
• Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002 Sep 24;106(12 Suppl 1):I109-14.
• Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, Wagner JE, Kurtzberg J. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb;12(2):184-94. doi: 10.1016/j.bbmt.2005.09.016.
• Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest. 2005 Oct;115(10):2592-7. doi: 10.1172/JCI26690.
• Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med. 2004 May 6;350(19):1960-9. doi: 10.1056/NEJMoa032613.
• McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul;236(1):221-30. doi: 10.1148/radiol.2353040716.

Helpful Links

• Carolinas Cord Blood Bank web page

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): April 15, 2016
• Study Completion (Actual): April 15, 2016

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 29, 2011
• First Posted (Estimated): October 3, 2011

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Hypoplastic Left Heart Syndrome; Autologous Umbilical Cord Blood; Newborn Infants
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Syndrome; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: Pro00024650