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

Phase 1
Completed
Conditions
Hypoplastic Left Heart Syndrome
Interventions
Biological: autologous cell-based delivery
Registration Number
NCT01883076
Lead Sponsor
Timothy J Nelson, MD, PhD
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 Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
autologous cell-based deliveryautologous cell-based deliveryautologous cell-based delivery a target dose of 3 million cells / kg of body weight will be delivered into the right heart muscle at the time of surgery. Cells are derived from autologous (self) umbilical cord blood.
Primary Outcome Measures
NameTimeMethod
Incidence of new and worsening adverse cardiac eventsWithin 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 enrolled who undergo cell therapy treatmentUp to 2 years
Incidence of all-cause mortalityWithin 2 years following cell therapy treatment
Percentage of subjects whose cells meet all cell release criteriaUp to 2 years
Secondary Outcome Measures
NameTimeMethod
Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiographybaseline, 3 months
Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiographybaseline, 1 month
Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiographybaseline, 6 months
Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiographybaseline, 6 months
Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiographybaseline, 1 month
Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiographybaseline, 6 months
Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiographybaseline, 3 months
Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiographybaseline, 3 months
Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiographybaseline, 1 month

Trial Locations

Locations (6)

Children's Hospital of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Oklahoma University Children's Hospital

🇺🇸

Oklahoma City, Oklahoma, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

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