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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypoplastic Left Heart Syndrome
• Intervention / Treatment: Biological: Autologous (self) mononuclear cells derived from umbilical cord blood; Procedure: Stage II Surgical repair

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ocshner Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals of Minnesota
  • Ohio
    • Cincinnati, Ohio, United States, 45529
      • Cincinnati Children's Hospital and Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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.

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline, 3 months post-Stage II surgery
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.	baseline, 3 months post-Stage II surgery
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.	baseline, 3 months post-Stage II surgery
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.	baseline, 12 months post-Stage II surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)
Cumulative Days of Hospitalization	Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.	1-month post Stage II surgery
Change in Weight	Change in weight between baseline and 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.	baseline, 3-months post Stage II surgery
Change in Heart Rate	Change in heart rate between baseline and 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.	baseline, 3-months post Stage II surgery
Change in Oxygen Saturation	Change in oxygen saturation between baseline and 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.	baseline, 3-months post Stage II surgery
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.	baseline, every 6 months post-Stage II surgery
Change in Arrhythmia and Heart Failure Medication	Changes in arrhythmia and 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.	3-months post-surgery
Stage III Surgical Repair	The number of research subjects eligible for Stage III surgical repair	Stage III surgery pre-op, approx. 4 years
Total Time Until Listed for Cardiac Transplantation	The number of days between Stage II surgery and listed on cardiac transplantation list.	up to Stage III surgery pre-op, approx. 4 years
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.	baseline, Stage III surgery pre-op
Total Time Until Death	The number of days between Stage II surgery and death occurrence	approx 4 years
Cumulative Days of Hospitalization	Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.	3-months post Stage II surgery

Collaborators and Investigators

• Sponsor: Timothy J Nelson, MD, PhD
• Collaborators: 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: James Tweddell, M.D., Children's Hospital Medical Center, Cincinnati; Principal Investigator: Ram Kumar Subramanyan, M.D., Ph.D., Children's Hospital Los Angeles; Principal Investigator: James Jaggers, M.D., Children's Hospital Colorado; 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: Benjamin Peeler, M.D., Ochsner Health System; Principal Investigator: Waldemar Carlo, M.D., University of Alabama at Birmingham

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): May 22, 2022
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 15, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Stem cells; Congenital Heart Disease; Umbilical Cord Blood; Cord blood; HLHS; Regenerative therapy; Hypoplastic Left Heart Syndrome; UCB; single ventricle; Stage II Glenn; Glenn Surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Syndrome; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: 18-004753

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