Clinical Trial: Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome

Brief Summary:

This is a Phase I study to determine the safety and feasibility of injections of autologous umbilical cord blood (UCB) cells into the right ventricle of Hypoplastic Left Heart Syndrome (HLHS) children undergoing a scheduled Glenn surgical procedure.

The investigators are doing this research study to find out if autologous stem cells from the individual's own umbilical cord blood can be used to strengthen the muscle of the right side of their heart. This will help determine the safety and feasibility of using cell-based regenerative therapy as an additional treatment for the management of HLHS.

Detailed Summary: This study is a Phase I trial to determine the safety of autologous mononuclear cells (MNC) derived from umbilical cord blood for intramyocardial delivery into the right ventricle during a planned and non-emergent Stage II surgical palliation in subjects with HLHS. This is the first critical step towards applying autologous MNC therapy as an add-on regenerative intervention for congenital heart disease management. The choice of HLHS as the target disease for regenerative therapies in congenital heart disease management is multi-factorial and includes the following considerations: 1) Severity of of this incurable disease, 2) palliative nature and burden of long-term outcomes with a single right ventricular system, 3) three stages of planned surgical procedures that provide time points to adjunctively intervene, and 4) prenatal diagnosis enabling planned collection of UCB. An emerging goal for cardiac regeneration includes the application of cell-based technology to congenital heart disease, which is a favorable substrate due to the lack of fibrotic scaring, and the presence of a microenvironment that is expected to support ongoing cardiac proliferation and growth for functional remuscularization. This Phase I safety study will determine the feasibility of collection, processing, and delivery of autologous cells as used in adult cardiac regenerative protocols in the setting of HLHS surgical management.
Sponsor: Timothy J. Nelson

Current Primary Outcome:

• Incidence of all-cause mortality [ Time Frame: Within 2 years following cell therapy treatment ]
• Incidence of new and worsening adverse cardiac events [ Time Frame: Within 2 years following cell therapy treatment ]
  The adverse cardiac events would include sustained/symptomatic ventricular arrhythmias, heart failure, myocardial infarction, cardiac infections, and unexpected cardiovascular surgery.
• Percentage of subjects whose cells meet all cell release criteria [ Time Frame: Up to 2 years ]
• Percentage of subjects enrolled who undergo cell therapy treatment [ Time Frame: Up to 2 years ]

Original Primary Outcome:

• Number of patients completing consent, collection of umbilical cord blood, and intramyocardial delivery of autologous stem cells [ Time Frame: 1 week post Glenn procedure ]
  The percentage of patients consented for the study that have successfully undergone umbilical cord blood collection, completed GMP-processing to meet release criteria, and achieved uncomplicated intramyocardial cell delivery will determine the feasibility of this approach.
• Number of patients with cardiac-related adverse events [ Time Frame: up to 6 months follow-up post Glenn procedure ]
  Upon intramyocardial cell delivery at the time of planned Glenn procedure, signs of cardiac toxicity will be measured according to worsening of ejection fraction by more than 10%, any new cardiac arrhythmias that could be attributed to stem cell therapy based on follow-up electrocardiograms and 24-hr Holter monitoring, and abnormal routine blood chemistry to monitor for evidence of organ failure.

Current Secondary Outcome:

• Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
• Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
• Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
• Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
• Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
• Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
• Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
• Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
• Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]

Original Secondary Outcome: Change in right ventricular ejection fraction according to cardiac imaging with echocardiography [ Time Frame: 6 months follow-up post Glenn procedure ]

Dates:
Date Received: June 11, 2013
Date Started: May 2013
Date Completion: December 2017
Last Updated: October 25, 2016
Last Verified: October 2016