Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome
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 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.
Hypoplastic Left Heart Syndrome
Biological: autologous cell-based delivery
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome|
- Number of patients completing consent, collection of umbilical cord blood, and intramyocardial delivery of autologous stem cells [ Time Frame: 1 week post Glenn procedure ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]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.
- Change in right ventricular ejection fraction according to cardiac imaging with echocardiography [ Time Frame: 6 months follow-up post Glenn procedure ] [ Designated as safety issue: No ]The secondary analysis is focused on the potential benefit of intramyocardial delivery of the manufactured cell-based product in pediatric hearts at the time of planned surgical palliation for HLHS. The change from baseline to 1, 3, and 6-month follow-up in right ventricular ejection fraction is the primary variable along with secondary variables of change in right ventricle TAPSE and fractional area change.
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: autologous cell-based delivery
autologous 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.
Biological: autologous cell-based delivery
autologous cells (derived from "self")
Other Name: umbilical cord blood derived mononuclear cells
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01883076
|Contact: Julia M Thebiay||(507) firstname.lastname@example.org|
|Contact: Karen P Krucker, RN||(507) email@example.com|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Julia Thebiay 507-538-8425 firstname.lastname@example.org|
|Principal Investigator: Timothy J Nelson, M.D., Ph.D.|
|Principal Investigator:||Timothy J Nelson, M.D., Ph.D.||Mayo Clinic|