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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04907526
Recruitment Status : Recruiting
First Posted : May 28, 2021
Last Update Posted : May 4, 2022
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Timothy J Nelson, MD, PhD, ReGen Theranostics, Inc.

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.

Condition or disease Intervention/treatment Phase
Congenital Heart Disease, SRV Dependent Biological: Autologous mononuclear cells Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : June 30, 2024


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.



Primary Outcome Measures :
  1. Short-term safety [ Time Frame: Within 3 months post Fontan surgery ]
    Measure of new or worsening adverse events


Secondary Outcome Measures :
  1. Long term safety [ Time Frame: Within 2 years post Fontan surgery ]
    Measure of new or worsening adverse events

  2. Right ventricular function [ Time Frame: 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

  3. High sensitivity Troponin T [ Time Frame: 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

  4. NT-pro-BNP [ Time Frame: 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

  5. Panel Reactive Antibody [ Time Frame: 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.

  6. Weight [ Time Frame: Baseline, 3 months post-Fontan surgery, 12 months post-Fontan surgery ]
    Change from baseline in weight at 3 and 12 months post-Fontan surgery.

  7. Cumulative days hospitalization [ Time Frame: 3 months post discharge, 12 months post discharge ]
    Cumulative days of hospitalization per patient at 3 and 12 months post-Fontan surgery discharge

  8. PROMIS Parent Proxy Scale v1.0-Global Health 7 [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04907526


Contacts
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Contact: Lynn Padley 5075771764 lynn@regentheranostics.com

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Ram Kumar Subramanyan, M.D.    323-361-4148    rsubramanyan@chla.usc.edu   
Contact: Brandi Scott    323-361-7086    bscott@chla.usc.edu   
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: James Jaggers, MD    720-777-3376    James.Jaggers@childrenscolorado.org   
Contact: Molly Brown    720-777-5828    molly.brown@childrenscolorado.org   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Joseph Dearani, M.D    507-255-2034    jdearani@mayo.edu   
Contact: Lori Riess    507-538-7730    riess.lori@mayo.edu   
Principal Investigator: Joseph Dearani, M.D.         
United States, Oklahoma
University of Oklahoma Medical Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Harold M Burkhart, M.D.    405-271-4505    Harold-Burkart@ouhsc.edu   
Contact: David Alexander    405-271-1194    david-alexander@ouhsc.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph W Rossano, MD    267-426-7518    RossanoJ@email.chop.edu   
Contact: Baotram Nguyen    610-698-4554    nguyenb4@chop.edu   
Sponsors and Collaborators
Timothy J Nelson, MD, PhD
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
Investigators
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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
Additional Information:
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Responsible Party: Timothy J Nelson, MD, PhD, Program Director, ReGen Theranostics, Inc.
ClinicalTrials.gov Identifier: NCT04907526    
Other Study ID Numbers: 21-000088
First Posted: May 28, 2021    Key Record Dates
Last Update Posted: May 4, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Timothy J Nelson, MD, PhD, ReGen Theranostics, Inc.:
Hypoplastic Left Heart Syndrome
HLHS
Congenital Heart Disease
Umbilical Cord Blood
UCB
Cord Blood
Stem Cells
Regenerative therapy
Stage III Fontan
Fontan surgery
Additional relevant MeSH terms:
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Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities