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

NCT03779711 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-004753
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC)

  baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)

• Cumulative Days of Hospitalization

  1-month post Stage II surgery

• Change in Weight

  baseline, 3-months post Stage II surgery

• Change in Heart Rate

  baseline, 3-months post Stage II surgery

• Change in Oxygen Saturation

  baseline, 3-months post Stage II surgery

Study Arms (2)

Treatment

EXPERIMENTAL

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; Procedure: Stage II Surgical repair

Control

ACTIVE COMPARATOR

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

Interventions

Autologous (self) mononuclear cells derived from umbilical cord blood BIOLOGICAL

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.

Treatment

Stage II Surgical repair PROCEDURE

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.

Control; Treatment

Eligibility Criteria

• Age: Up to 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Timothy J Nelson, MD, PhD: lead
• University of Oklahoma: collaborator
• Children's Hospital of Philadelphia: collaborator
• Children's Hospital Los Angeles: collaborator
• Children's Hospital Colorado: collaborator
• Children's Hospitals and Clinics of Minnesota: collaborator
• Ochsner Health System: collaborator
• Children's of Alabama: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (8)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Ocshner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Children's Hospitals of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Cincinnati Children's Hospital and Medical Center

Cincinnati, Ohio, 45529, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Gallego-Navarro C, Jaggers J, Burkhart HM, Carlo WF, Morales DL, Qureshi MY, Rossano JW, Hagen CE, Seisler DK, Peral SC, Nelson TJ. Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and safety of intramyocardial injections. Stem Cell Res Ther. 2025 May 1;16(1):215. doi: 10.1186/s13287-025-04316-3.

  PMID: 40312733 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Heart Defects, Congenital; Univentricular Heart

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Clint Hagen
• Organization: Mayo Clinic

hagen.clint@mayo.edu

(507) 577-1764

Study Officials

• 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 Kumar Subramanyan, M.D., Ph.D.

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

• James Jaggers, M.D.

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

• Benjamin Peeler, M.D.

  Ochsner Health System

  PRINCIPAL INVESTIGATOR

• Waldemar Carlo, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• James Tweddell, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Program Director

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: December 19, 2018
• Study Start: June 6, 2019
• Primary Completion: May 22, 2022
• Study Completion: February 1, 2026
• Last Updated: July 8, 2025
• Results First Posted: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)