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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Heart Disease, SRV Dependent
• Intervention / Treatment: Biological: Autologous mononuclear 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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lynn Padley; Phone Number: 5075771764; Email: lynn@regentheranostics.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; 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; Autologous mononuclear cells delivered into right ventricle at time of Stage III Fontan surgery.
No Intervention: Control Arm; 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?

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

Collaborators and Investigators

• Sponsor: Timothy J Nelson, MD, PhD
• Collaborators: The Hospital for Sick Children; Mayo Clinic; Children's Hospital of Philadelphia; Children's Hospital Colorado; University of Oklahoma; Children's Hospital Medical Center, Cincinnati; Children's Hospitals and Clinics of Minnesota; Children's Hospital Los Angeles; Ochsner Health System; Children's of Alabama
• Investigators: Principal Investigator: Joseph Dearani, Mayo Clinic; Principal Investigator: Harold M Burkhart, Children's Hospital Oklahoma University Medical Center; Principal Investigator: Joseph w Rossano, Children's Hospital of Philadelphia; Principal Investigator: David M Overman, Children's Minnesota; Principal Investigator: Ram Kumar Subramanyan, MD, Children's Hospital Los Angeles; Principal Investigator: James Jaggers, MD, Children's Hospital Colorado; Principal Investigator: Benjamin Peeler, MD, Ochsner Health System; Principal Investigator: Waldemer Carlo, M.D., University of Alabama at Birmingham; Principal Investigator: James Tweddell, M.D., Children's Hospital Medical Center, Cincinnati; Principal Investigator: Jason Maynes, MD, The Hospital forSick Children

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): May 24, 2023
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Congenital Heart Disease; Stem Cells; Umbilical Cord Blood; HLHS; Regenerative therapy; Hypoplastic Left Heart Syndrome; UCB; Cord Blood; Stage III Fontan; Fontan surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 21-000088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No