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

Primary Purpose

Congenital Heart Disease, SRV Dependent

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous mononuclear cells
Sponsored by
Timothy J Nelson, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Heart Disease, SRV Dependent focused on measuring Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord Blood, Stem Cells, Regenerative therapy, Stage III Fontan, Fontan surgery

Eligibility Criteria

2 Years - 5 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama Medical CenterRecruiting
  • Children's Hospital Los AngelesRecruiting
  • Children's Hospital ColoradoRecruiting
  • Mayo ClinicRecruiting
  • University of Oklahoma Medical CenterRecruiting
  • Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment Arm

Control Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Short-term safety
Measure of new or worsening adverse events

Secondary Outcome Measures

Long term safety
Measure of new or worsening adverse events
Right ventricular function
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
Change from baseline in High sensitivity Troponin T at 3 hours and 6 hours after enrollment and at hospital discharge
NT-pro-BNP
Change from baseline in NT-pro-BNP levels compared to baseline, at hospital discharge and at 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.
Weight
Change from baseline in weight at 3 and 12 months post-Fontan surgery.
Cumulative days hospitalization
Cumulative days of hospitalization per patient at 3 and 12 months post-Fontan surgery 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

Full Information

First Posted
May 12, 2021
Last Updated
January 9, 2023
Sponsor
Timothy J Nelson, MD, PhD
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
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1. Study Identification

Unique Protocol Identification Number
NCT04907526
Brief Title
Intramyocardial Injection of Autologous UCB-MNC During Fontan Surgery for SRV Dependent CHD
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Timothy J Nelson, MD, PhD
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Heart Disease, SRV Dependent
Keywords
Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord Blood, Stem Cells, Regenerative therapy, Stage III Fontan, Fontan surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Control Arm
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Autologous mononuclear cells
Intervention Description
Autologous mononuclear cells delivered into right ventricle at time of Stage III Fontan surgery.
Primary Outcome Measure Information:
Title
Short-term safety
Description
Measure of new or worsening adverse events
Time Frame
Within 3 months post Fontan surgery
Secondary Outcome Measure Information:
Title
Long term safety
Description
Measure of new or worsening adverse events
Time Frame
Within 2 years post Fontan surgery
Title
Right ventricular function
Description
Change from baseline Transthoracic Echocardiogram right ventricular function as measured by biplane Fractional Area Change (FAC) at discharge and 3 months
Time Frame
Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
Title
High sensitivity Troponin T
Description
Change from baseline in High sensitivity Troponin T at 3 hours and 6 hours after enrollment and at hospital discharge
Time Frame
3 hours post enrollment, 6 hours post enrollment, hospital discharge (up to 30 days post Fontan surgery)
Title
NT-pro-BNP
Description
Change from baseline in NT-pro-BNP levels compared to baseline, at hospital discharge and at 3 months post-Fontan surgery
Time Frame
Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
Title
Panel Reactive Antibody
Description
Change from baseline in PRA levels at discharge and 3 months post-Fontan surgery compared to baseline.
Time Frame
Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months post Fontan surgery
Title
Weight
Description
Change from baseline in weight at 3 and 12 months post-Fontan surgery.
Time Frame
Baseline, 3 months post-Fontan surgery, 12 months post-Fontan surgery
Title
Cumulative days hospitalization
Description
Cumulative days of hospitalization per patient at 3 and 12 months post-Fontan surgery discharge
Time Frame
3 months post discharge, 12 months post discharge
Title
PROMIS Parent Proxy Scale v1.0-Global Health 7
Description
Change from baseline in PROMIS Parent Proxy Scale v1.0-Global Health 7 at discharge, 3, 12, 18, and 24 months post-Fontan surgery
Time Frame
Baseline, hospital discharge (up to 30 days post Fontan surgery), 3 months, 12 months, 18 months, 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lynn Padley
Phone
5075771764
Email
lynn@regentheranostics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Dearani
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harold M Burkhart
Organizational Affiliation
Children's Hospital Oklahoma University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph w Rossano
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David M Overman
Organizational Affiliation
Children's Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ram Kumar Subramanyan, MD
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Jaggers, MD
Organizational Affiliation
Children's Hospital Colorado
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Benjamin Peeler, MD
Organizational Affiliation
Ochsner Health System
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Waldemer Carlo, M.D.
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Tweddell, M.D.
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jason Maynes, MD
Organizational Affiliation
The Hospital forSick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Medical Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Waldemar Carlo, M.D.
Phone
205-638-2018
Email
wfcarlo@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Krissie Hock
Phone
205-996-3313
Email
kristalhock@uabmc.edu
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ram Kumar Subramanyan, M.D.
Phone
323-361-4148
Email
rsubramanyan@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Brandi Scott
Phone
323-361-7086
Email
bscott@chla.usc.edu
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Jaggers, MD
Phone
720-777-3376
Email
James.Jaggers@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Molly Brown
Phone
720-777-5828
Email
molly.brown@childrenscolorado.org
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Dearani, M.D
Phone
507-255-2034
Email
jdearani@mayo.edu
First Name & Middle Initial & Last Name & Degree
Lori Riess
Phone
507-538-7730
Email
riess.lori@mayo.edu
First Name & Middle Initial & Last Name & Degree
Joseph Dearani, M.D.
Facility Name
University of Oklahoma Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Harold M Burkhart, M.D.
Phone
405-271-4505
Email
Harold-Burkart@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
David Alexander
Phone
405-271-1194
Email
david-alexander@ouhsc.edu
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph W Rossano, MD
Phone
267-426-7518
Email
RossanoJ@email.chop.edu
First Name & Middle Initial & Last Name & Degree
Baotram Nguyen
Phone
610-698-4554
Email
nguyenb4@chop.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

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