Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single Ventricle Physiology

Study Overview
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Brief Summary
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Hypoplastic left heart syndrome (HLHS) and related anomalies involved a single ventricle are characterized by hypoplasia of the left heart and the aorta with compromised systemic cardiac output. Infants with the syndrome generally undergo a staged surgical approach in view of an ultimate Fontan procedure. Although long-term survival in patients with HLHS and related single ventricle physiology has improved markedly with advances in medical and surgical therapies, a growing number of infants will ultimately require heart transplantation for end-stage heart failure due to several potential disadvantages include a negative effect on right ventricular function, arrhythmia, additional volume load via regurgitation from the nonvalved shunt, and impaired growth of the pulmonary artery. Risk factors for poor outcome of heart transplantation with HLHS and single ventricle physiology are older age at transplantation and previous Fontan operation. New strategies are needed to improve the underlying transplant risks proper for the Fontan failure patients. Emerging evidence suggests that heart-derived stem/progenitor cells can be used to improved cardiac function in patients with ischemic heart disease. In this trial, the investigators aimed to test the safety and feasibility of intracoronary injection of autologous cardiac progenitor cells in patients with HLHS and related single ventricle anomalies and that could improve ventricular function at 3 months' follow up.

Detailed Description
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Autologous cardiac progenitor cells are isolated from patients' own cardiac tissues obtained during palliative shunt procedure. Patients will receive 0.3 million/kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.

Official Title
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Phase I Study of Cardiac Progenitor Cell Therapy in Patients With Single Ventricle Physiology

Conditions
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Hypoplastic Left Heart Syndrome, Single Ventricle, Heart Failure

Intervention / Treatment
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* Procedure: Autologous cardiac progenitor cell transplantation
* Procedure: staged shunt procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants with hypoplastic left heart syndrome and related single ventricle anomalies undergoing first to third palliative shunt surgeries will be recruited into the study. Patients between 0 and 6 years of age are eligible if written informed consent can be obtained. Exclusion Criteria: Cardiogenic shock Eisenmenger syndrome Uncontrollable arrhythmia Severe chronic diseases Infections Cancer Unwillingness to participate

Ages Eligible for Study
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Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control<br>Subjects will undergo standard staged-procedures without cell infusion | Procedure: staged shunt procedure<br>* Norwood-Glenn, Glenn, or Fontan procedure will be applied<br>|
| Experimental: Cell infusion<br>Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure | Procedure: Autologous cardiac progenitor cell transplantation<br>* Patients will receive 0.3 million / kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.<br>* Other names: Cardiosphere-derived cells;Procedure: staged shunt procedure<br>* Norwood-Glenn, Glenn, or Fontan procedure will be applied<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells | Feasibility was assessed by number of participants discontinued the study due to adverse events or number of participants received unsuccessful cell delivery by study physician. Unsuccessful was defined as failure of coronary selection of guiding catheter or direct cell infusion. The primary end point is to monitor major adverse cardiac events include death, sustained/symptomatic ventricular tachycardia, aggravation of heart failure, new myocardial infarction, unplanned cardiovascular operation for cardiac tamponade and infection in the first month after injection, and serially afterwards. | 3 months to 1 year after cell transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events | The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment. | 3 months to 1 year after cell transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac progenitor cells, Cell therapy, Hypoplastic Left Heart Syndrome, Single Ventricle, Norwood, Sano modification, Glenn, Fontan