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Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Repair of Hypoplastic Left Heart Syndrome (AutoCell-S2)

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ClinicalTrials.gov Identifier: NCT03779711
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : March 11, 2019
Sponsor:
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
Information provided by (Responsible Party):
Timothy J. Nelson, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Hypoplastic Left Heart Syndrome Biological: Autologous (self) mononuclear cells derived from umbilical cord blood Procedure: Stage II Surgical repair Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2026


Arm Intervention/treatment
Experimental: Treatment
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 .
Biological: Autologous (self) mononuclear cells derived from umbilical cord blood
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.

Procedure: Stage II Surgical repair
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.

Active Comparator: Control
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.
Procedure: Stage II Surgical repair
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 Measures :
  1. Change in Right Ventricular Ejection Fraction [ Time Frame: baseline, 3 months post-Stage II surgery ]
    Right ventricular ejection fraction as measured by cardiac MRI. 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.

  2. Change in Right Ventricular Ejection Fraction [ Time Frame: baseline, 12 months post-Stage II surgery ]
    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 :
  1. Change in ejection fraction [ Time Frame: baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks) ]
    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.

  2. Cumulative days of hospitalization [ Time Frame: 1, 3-months post Stage II surgery ]
    Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.

  3. Change in weight [ Time Frame: 1, 3-months post Stage II surgery ]
    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.

  4. Change in heart rate [ Time Frame: 1, 3-months post Stage II surgery ]
    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.

  5. Change in oxygen saturation [ Time Frame: 1, 3-months post Stage II surgery ]
    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.

  6. Change in weight [ Time Frame: baseline, every 6 months post-Stage II surgery ]
    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.

  7. Change in heart failure medication [ Time Frame: baseline, every 6 months post-Stage II surgery ]
    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.

  8. Change in arrhythmia medication [ Time Frame: baseline, every 6 months post-Stage II surgery ]
    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.

  9. Stage III surgical repair [ Time Frame: Stage III surgery pre-op, approx. 4 years ]
    The number of research subjects eligible for Stage III surgical repair

  10. Total time until listed for cardiac transplantation [ Time Frame: up to Stage III surgery pre-op, approx. 4 years ]
    The number of days between Stage II surgery and listed on cardiac transplantation list.

  11. Change in right ventricular ejection fraction [ Time Frame: baseline, Stage III surgery pre-op ]
    Right ventricular ejection fraction as measured by echocardiogram, cardiac MRI, 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.

  12. Total time until death [ Time Frame: approx 4 years ]
    The number of days between Stage II surgery and death occurrence



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Ages Eligible for Study:   up to 8 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Child that participated in the UCB Collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only).
  • Child with HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and Stage II surgical repair.
  • Child is < 9 months of age.

Exclusion Criteria:

  • History of DMSO reaction for either the child or mother (treatment arm only).
  • Parent(s) and/or guardian(s) unwilling to have their child participate or unwilling to follow the study procedures.
  • Child with severe chronic diseases at the discretion of the treating physician.
  • Extensive extra-cardiac syndromic features.
  • Known history of cancer.
  • Child with the following complications of their congenital heart disease:

    1. Any condition requiring urgent, or unplanned 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 during or after Stage II surgical repair.

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): NCT03779711


Contacts
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Contact: Sarah Hanson 507-272-3835 sarah@regentheranostics.com
Contact: Natalie Wegner 507-951-2209 natalie@regnentheranostics.com

Locations
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United States, California
Children's Hospital of Los Angeles Not yet recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Ram Kuma Subramanyan, M.D.         
United States, Colorado
Children's Hospital Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: James Jaggers, M.D.         
United States, Minnesota
Children's Hospitals of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55404
Principal Investigator: David M Overman, M.D.         
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Frank Cetta, MD         
United States, Oklahoma
Children's Hospital Oklahoma University Medical Center Not yet recruiting
Oklahoma City, Oklahoma, United States, 73104
Principal Investigator: Harold M Burkhart, M.D.         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Joseph W Rossano, M.D.         
Sponsors and Collaborators
Timothy J. Nelson
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospital Los Angeles
Children's Hospital Colorado
Children's Hospitals and Clinics of Minnesota
Investigators
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Principal Investigator: Frank Cetta, MD Mayo Clinic
Principal Investigator: Harold M. Burkhart, M.D. Children's Hospital Oklahoma University Medical Center
Principal Investigator: Joseph W. Rossano, M.D. Children's Hospital of Philadelphia
Principal Investigator: David M. Overman, M.D. Children's Minnesota
Principal Investigator: Ram Kuma Subramanyan, M.D., Ph.D. Children's Hospital Los Angeles
Principal Investigator: James Jaggers, M.D. Children's Hospital Colorado

Additional Information:
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Responsible Party: Timothy J. Nelson, Associate Professor of Medicine and Pharmacology, College of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03779711     History of Changes
Other Study ID Numbers: 18-004753
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019

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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, Mayo Clinic:
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

Additional relevant MeSH terms:
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Syndrome
Hypoplastic Left Heart Syndrome
Disease
Pathologic Processes
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities