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Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome

Primary Purpose

Hypoplastic Left Heart Syndrome

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Autologous (self) mononuclear cells derived from umbilical cord blood
Stage II Surgical repair
Sponsored by
Timothy J Nelson, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoplastic Left Heart Syndrome focused on measuring Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle

Eligibility Criteria

undefined - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair.
  • Less than 13 months of age at time of Stage II surgical repair
  • Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only)

Exclusion Criteria:

  • History of DMSO reaction (treatment arm only).
  • Parent(s) and/or legal guardian(s) 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.
  • Known history of cancer.
  • Any of the following complications of his/her congenital heart disease:

    1. Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, unless complete and full cardiac recovery is documented by site investigator
    2. Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure)
    3. 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 to the stem cell product or its injection procedure, during or after Stage II surgical repair.

Sites / Locations

  • Children's of Alabama
  • Children's Hospital of Los Angeles
  • Children's Hospital Colorado
  • Ocshner Medical Center
  • Children's Hospitals of Minnesota
  • Cincinnati Children's Hospital and Medical Center
  • Oklahoma University Medical Center
  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment

Control

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 1-3 million cells per kilogram body weight . This is a one time treatment at the time of Stage II Glenn surgery .

Clinical data will be collected before, during and after the Stage II surgical standard of care procedure. Requires additional imaging studies at 3 months that are not standard of care in addition to some blood tests that would be beyond standard of care. Information will be collected to document the clinical outcomes and will be compared with the information from the group receiving the investigational treatment used in this study.

Outcomes

Primary Outcome Measures

Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC)
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Change in Right Ventricular Cardiac Function measured by circumferential strain.
Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent.
Change in Right Ventricular Cardiac Function measured by longitudinal strain.
Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent.
Change in Right Ventricular Ejection Fraction
Right ventricular ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.

Secondary Outcome Measures

Change in ejection fraction
Ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.
Cumulative days of hospitalization
Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.
Change in weight
Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Change in heart rate
Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform.
Change in oxygen saturation
Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation.
Change in weight
Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Change in heart failure medication
Changes in heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.
Change in arrhythmia medication
Changes in arrhythmia medication will be recorded by subject's caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.
Stage III surgical repair
The number of research subjects eligible for Stage III surgical repair
Total time until listed for cardiac transplantation
The number of days between Stage II surgery and listed on cardiac transplantation list.
Change in right ventricular function
Right ventricular ejection fraction as measured by echocardiogram, and cardiac catheterization. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.
Total time until death
The number of days between Stage II surgery and death occurrence

Full Information

First Posted
December 4, 2018
Last Updated
May 5, 2023
Sponsor
Timothy J Nelson, MD, PhD
Collaborators
University of Oklahoma, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Children's Hospital Colorado, Children's Hospitals and Clinics of Minnesota, Ochsner Health System, Children's of Alabama, Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT03779711
Brief Title
Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome
Official Title
Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Stage II Surgical Repair of Right Ventricular Dependent Variants of Hypoplastic Left Heart Syndrome (AutoCell-S2)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 6, 2019 (Actual)
Primary Completion Date
May 22, 2022 (Actual)
Study Completion Date
February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Timothy J Nelson, MD, PhD
Collaborators
University of Oklahoma, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Children's Hospital Colorado, Children's Hospitals and Clinics of Minnesota, Ochsner Health System, Children's of Alabama, Children's Hospital Medical Center, Cincinnati

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 stem cells are injected directly into the muscle of the right side of the heart during the Stage II palliative surgery for single ventricle patients with hypoplastic left heart syndrome (HLHS) or HLHS variant. Researchers want to see if there are changes in the heart's structure/function following this stem cell-based therapy and compared to children that have not had cell-based therapy.
Detailed Description
This is a Phase IIb trial to determine if the delivery of the autologous UCB-MNC product into the myocardium of the right ventricle of the heart at the time of Stage II surgical repair will provide an improvement in cardiac function, reaching growth and developmental milestones, and quality of life, while also providing a reduction in the cumulative days of hospitalization following Stage II surgical repair. Long-term improvement in cardiac function, reaching growth and developmental milestones, reaching Stage III surgical repair pre-op work-up, prolonging time to cardiac transplantation or death, and improving quality of life will also be determined.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoplastic Left Heart Syndrome
Keywords
Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
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 1-3 million cells per kilogram body weight . This is a one time treatment at the time of Stage II Glenn surgery .
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Clinical data will be collected before, during and after the Stage II surgical standard of care procedure. Requires additional imaging studies at 3 months that are not standard of care in addition to some blood tests that would be beyond standard of care. Information will be collected to document the clinical outcomes and will be compared with the information from the group receiving the investigational treatment used in this study.
Intervention Type
Biological
Intervention Name(s)
Autologous (self) mononuclear cells derived from umbilical cord blood
Intervention Description
The investigational product will be delivered into the right myocardium via sub-epicardial injections of 0.1 mL per kg body weight to achieve the target dose of 1-3 million TNC per kg body weight.at the time of Stage II surgical repair.
Intervention Type
Procedure
Intervention Name(s)
Stage II Surgical repair
Intervention Description
This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle.
Primary Outcome Measure Information:
Title
Change in Right Ventricular Cardiac Function measured by apical fractional area change (FAC)
Description
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Time Frame
baseline, 3 months post-Stage II surgery
Title
Change in Right Ventricular Cardiac Function measured by circumferential strain.
Description
Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent.
Time Frame
baseline, 3 months post-Stage II surgery
Title
Change in Right Ventricular Cardiac Function measured by longitudinal strain.
Description
Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent.
Time Frame
baseline, 3 months post-Stage II surgery
Title
Change in Right Ventricular Ejection Fraction
Description
Right ventricular ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.
Time Frame
baseline, 12 months post-Stage II surgery
Secondary Outcome Measure Information:
Title
Change in ejection fraction
Description
Ejection fraction as measured by echocardiogram. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.
Time Frame
baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)
Title
Cumulative days of hospitalization
Description
Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.
Time Frame
1, 3-months post Stage II surgery
Title
Change in weight
Description
Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Time Frame
3-months post Stage II surgery
Title
Change in heart rate
Description
Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform.
Time Frame
3-months post Stage II surgery
Title
Change in oxygen saturation
Description
Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation.
Time Frame
3-months post Stage II surgery
Title
Change in weight
Description
Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Time Frame
baseline, every 6 months post-Stage II surgery
Title
Change in heart failure medication
Description
Changes in heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.
Time Frame
baseline, every 6 months post-Stage II surgery
Title
Change in arrhythmia medication
Description
Changes in arrhythmia medication will be recorded by subject's caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.
Time Frame
baseline, every 6 months post-Stage II surgery
Title
Stage III surgical repair
Description
The number of research subjects eligible for Stage III surgical repair
Time Frame
Stage III surgery pre-op, approx. 4 years
Title
Total time until listed for cardiac transplantation
Description
The number of days between Stage II surgery and listed on cardiac transplantation list.
Time Frame
up to Stage III surgery pre-op, approx. 4 years
Title
Change in right ventricular function
Description
Right ventricular ejection fraction as measured by echocardiogram, and cardiac catheterization. Ejection Fraction is calculated by the volume of blood in the heart during systole and diastole. It is the percentage of the volume in the ventricle ejected during a cardiac cycle. Measured by percent. The normal ejection fraction is 55 to 75 percent.
Time Frame
baseline, Stage III surgery pre-op
Title
Total time until death
Description
The number of days between Stage II surgery and death occurrence
Time Frame
approx 4 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair. Less than 13 months of age at time of Stage II surgical repair Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only) Exclusion Criteria: History of DMSO reaction (treatment arm only). Parent(s) and/or legal guardian(s) 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. Known history of cancer. Any of the following complications of his/her congenital heart disease: Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, 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 to the stem cell product or its injection procedure, during or after Stage II surgical repair.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Cetta, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harold M. Burkhart, M.D.
Organizational Affiliation
Children's Hospital Oklahoma University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph W. Rossano, M.D.
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David M. Overman, M.D.
Organizational Affiliation
Children's Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ram Kumar Subramanyan, M.D., Ph.D.
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Jaggers, M.D.
Organizational Affiliation
Children's Hospital Colorado
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Benjamin Peeler, M.D.
Organizational Affiliation
Ochsner Health System
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Waldemar 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
Facility Information:
Facility Name
Children's of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Ocshner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Children's Hospitals of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Cincinnati Children's Hospital and Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45529
Country
United States
Facility Name
Oklahoma University Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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

Learn more about this trial

Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome

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