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

Phase 1

Active, not recruiting

• Conditions: Congenital Heart Disease, SRV Dependent
• Interventions: Biological: Autologous mononuclear cells

• Registration Number: NCT04907526
• Lead Sponsor: Timothy J Nelson, MD, PhD

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.

Study Timeline

• Study First Submitted: 2021-05-12
• Study First Submitted QC: 2021-05-27
• Study First Posted: 2021-05-28
• Study Start: 2021-06-01
• Primary Completion: 2023-05-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-27
• Study Completion: 2025-08-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Autologous mononuclear cells	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.

Primary Outcome Measures

Name	Time	Method
Short-term safety	Within 3 months post Fontan surgery	Measure of new or worsening adverse events

Secondary Outcome Measures

Name	Time	Method
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
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
Long term safety	Within 2 years post Fontan surgery	Measure of new or worsening adverse events
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
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
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.
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.

Trial Locations

Locations (6)

University of Alabama Medical Center; 🇺🇸 Birmingham, Alabama, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Oklahoma Medical Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States