Intramyocardial Injection of Autologous UCB-MNC During Fontan Surgery for SRV Dependent CHD

Study Overview
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Brief Summary
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Researchers want to better understand what happens to the heart when the autologous (from one's own body) stem cells are injected directly into muscle of the right side of the heart during the Fontan (Stage III) surgery. They want to see if there are changes in the electrical activity, the structure, and the function of the heart following this stem cell-based therapy. Researchers will compare the results from people who receive the stem cells to the results from people who do not receive the stem cells.

Detailed Description
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This Phase I study is a multicenter, prospective, open-label, non-randomized study designed to evaluate the safety, of autologous UCB-MNC delivered into the right ventricular myocardium of subjects with severe CHD defined by single right ventricular dependent circulatory systems at the time of a planned Fontan surgical palliation. This will be achieved by comparing the data collected in the treatment arm to the equivalent data collected in the control arm. The purpose of this non-randomized open-label Phase I clinical study is to prospectively evaluate the safety, as measured by the short-term and long-term safety endpoints and change in baseline comparatives, for the autologous UCB-MNC intramyocardial injections into the single, morphologically right ventricle of subjects with severe CHD requiring Fontan surgical palliation. The treatment group will be compared to an untreated control group.

Official Title
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Phase I Study of Intramyocardial Injection of Autologous Umbilical Cord Blood-Derived Mononuclear Cells During Fontan Surgical Palliation of Single Right Ventricle-Dependent Congenital Heart Disease

Conditions
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Congenital Heart Disease, SRV Dependent

Intervention / Treatment
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* Biological: Autologous mononuclear cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a congenital hear defect with functionally single right ventricle (such as HLHS, HLHS variants, unbalanced AV septal defect with R dominance, DORV with Hypoplastic LV) undergoing Fontan surgical palliation At least 2 and less than or equal to 5 years of age at time of Fontan surgical palliation For subjects enrolling in the treatment arm, previous participation in clinical trial Umbilical Cord Blood Collection and Processing for Hypoplastic Left Heart Syndrome patients (NCT01856049) with autologous UCB-MNC product collected and available for distribution is required. Exclusion Criteria: History of DMSO reaction (treatment arm only subjects). Parent(s) or legal guardian unwilling to have their child participate or unwilling to follow the study procedures. Severe chronic diseases at the discretion of the treating physician. Extensive extra-cardiac syndromic features. History of cancer. Any of the following complications of his/her congenital heart disease: any condition requiring urgent, or unplanned intervention procedure within 15 days prior to Fontan surgical palliation, unless complete and full cardiac recovery is documented by site investigator. severe pulmonary hypertension (reported in the medical record as >70% systemic pressure) Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related tot he stem cell product or its injection procedure, during or after Fontan surgical palliation. Individuals with severe heart failure that requires heart transplantation Individuals with refractory or worsening arrhythmia Individuals with an automated implantable cardioverter defibrillator (AICD) or pacemaker Patient with prior surgical complications during the Fontan surgical palliation that resulted in or could be reasonably expected to significantly decrease cardiac function

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Autologous (self) mononuclear cells derived from umbilical cord blood and that meet all release criteria are injected into the surface of the right heart muscle to achieve the target dose of 3 million cells per kilogram of body weight. This is a one time treatment at the time of Stage III Fontan surgery. | Biological: Autologous mononuclear cells<br>* Autologous mononuclear cells delivered into right ventricle at time of Stage III Fontan surgery.<br>|
| No Intervention: Control Arm<br>Control cohort not receiving the cell product, which will be enrolled and followed using the same inclusion/exclusion criteria and follow-up requirements as the treatment arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term safety | Measure of new or worsening adverse events | Within 3 months post Fontan surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term safety | Measure of new or worsening adverse events | Within 2 years post Fontan surgery | 
| Right ventricular function | Change from baseline Transthoracic Echocardiogram right ventricular function as measured by biplane Fractional Area Change (FAC) at discharge and 3 months | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | 
| High sensitivity Troponin T | Change from baseline in High sensitivity Troponin T at 3 hours and 6 hours after enrollment and at hospital discharge | 3 hours post enrollment, 6 hours post enrollment, hospital discharge (up to 30 days post Fontan surgery) | 
| NT-pro-BNP | Change from baseline in NT-pro-BNP levels compared to baseline, at hospital discharge and at 3 months post-Fontan surgery | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | 
| Panel Reactive Antibody | Change from baseline in PRA levels at discharge and 3 months post-Fontan surgery compared to baseline. | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | 
| Weight | Change from baseline in weight at 3 and 12 months post-Fontan surgery. | Baseline, 3 months post-Fontan surgery, 12 months post-Fontan surgery | 
| Cumulative days hospitalization | Cumulative days of hospitalization per patient at 3 and 12 months post-Fontan surgery discharge | 3 months post discharge, 12 months post discharge | 
| PROMIS Parent Proxy Scale v1.0-Global Health 7 | Change from baseline in PROMIS Parent Proxy Scale v1.0-Global Health 7 at discharge, 3, 12, 18, and 24 months post-Fontan surgery | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months, 12 months, 18 months, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord Blood, Stem Cells, Regenerative therapy, Stage III Fontan, Fontan surgery