Congenital Heart Disease, SRV Dependent
Conditions
Keywords
Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord Blood, Stem Cells, Regenerative therapy, Stage III Fontan, Fontan surgery
Brief summary
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
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.
Interventions
BIOLOGICALAutologous mononuclear cells
Autologous mononuclear cells delivered into right ventricle at time of Stage III Fontan surgery.
Sponsors
Mayo Clinic
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospital Los Angeles
Children's Hospitals and Clinics of Minnesota
Children's Hospital Colorado
Ochsner Health System
Children's of Alabama
Children's Hospital Medical Center, Cincinnati
The Hospital for Sick Children
Timothy J Nelson, MD, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-term safety | Within 3 months post Fontan surgery | Measure of new or worsening adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Right ventricular function | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | Change from baseline Transthoracic Echocardiogram right ventricular function as measured by biplane Fractional Area Change (FAC) at discharge and 3 months |
| High sensitivity Troponin T | 3 hours post enrollment, 6 hours post enrollment, hospital discharge (up to 30 days post Fontan surgery) | Change from baseline in High sensitivity Troponin T at 3 hours and 6 hours after enrollment and at hospital discharge |
| NT-pro-BNP | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | Change from baseline in NT-pro-BNP levels compared to baseline, at hospital discharge and at 3 months post-Fontan surgery |
| Long term safety | Within 2 years post Fontan surgery | Measure of new or worsening adverse events |
| Weight | Baseline, 3 months post-Fontan surgery, 12 months post-Fontan surgery | Change from baseline in weight at 3 and 12 months post-Fontan surgery. |
| Cumulative days hospitalization | 3 months post discharge, 12 months post discharge | Cumulative days of hospitalization per patient at 3 and 12 months post-Fontan surgery discharge |
| PROMIS Parent Proxy Scale v1.0-Global Health 7 | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months, 12 months, 18 months, 24 months | Change from baseline in PROMIS Parent Proxy Scale v1.0-Global Health 7 at discharge, 3, 12, 18, and 24 months post-Fontan surgery |
| Panel Reactive Antibody | Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery | Change from baseline in PRA levels at discharge and 3 months post-Fontan surgery compared to baseline. |
Countries
United States
Outcome results
None listed