Stem Cell Therapy for Congenital Heart Disease

Recruiting at 5 trial locations

Overseen By Lynn Padley

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Timothy J Nelson, MD, PhD

Disqualifiers: Cancer, Severe heart failure, Arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Autologous Mononuclear Cells for Congenital Heart Disease?

Research shows that using stem cells, like those in Autologous Mononuclear Cells, has potential benefits for heart repair. In children with severe heart conditions, similar treatments have shown promise in improving heart function and may offer an option before considering a heart transplant. ^{1 2 3 4 5}

Is stem cell therapy using autologous mononuclear cells safe for humans?

Research shows that using autologous mononuclear cells, like those from umbilical cord blood, is generally safe in animal models, with no deaths or serious heart rhythm issues reported. Some minor, temporary heart rhythm changes were noted, likely due to anesthesia, but overall, the treatment was well-tolerated. ^{6 7 8 9 10}

How is the treatment with Autologous Mononuclear Cells different from other treatments for congenital heart disease?

This treatment uses the patient's own bone marrow cells to help repair the heart, which is different from standard treatments that often rely on medication or surgery. It offers a regenerative approach that may improve heart function and delay the need for a heart transplant. ^{4 5 7 10 11}

Research Team

Joseph W Rossano, M.D.

Principal Investigator

Children's Hospital of Philadelphia

Waldemer Carlo, M.D.

Principal Investigator

University of Alabama at Birmingham

James Tweddell, M.D.

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Jason Maynes, MD

Principal Investigator

The Hospital forSick Children

Ram Kumar Subramanyan, M.D.

Principal Investigator

Children's Hospital Los Angeles

James Jaggers, M.D.

Principal Investigator

Children's Hospital Colorado

Benjamin Peeler, MD

Principal Investigator

Ochsner Health System

Joseph Dearani, M.D

Principal Investigator

Mayo Clinic

Harold M Burkhart, M.D.

Principal Investigator

Children's Hospital Oklahoma University Medical Center

David M Overman, M.D.

Principal Investigator

Children's Minnesota

Eligibility Criteria

This trial is for children aged 2-5 with a specific heart defect (like HLHS) who are undergoing Fontan surgery. They must have previously participated in a related clinical trial and have their own stem cells available. Kids can't join if they've had severe reactions to certain preservatives, other serious chronic diseases, cancer, recent urgent procedures, or conditions that could worsen their outcome.

Inclusion Criteria

I have a single functioning right ventricle and am undergoing Fontan surgery.

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.

I had the Fontan surgery between 2 and 5 years old.

Exclusion Criteria

I need a heart transplant due to severe heart failure.

I haven't had any emergency procedures within 15 days before my Fontan surgery, or if I did, I've fully recovered.

Your doctor has other health concerns that could make the treatment risky for you.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intramyocardial injection of autologous UCB-MNC during Fontan surgery

1 day

1 visit (in-person)

Short-term Follow-up

Participants are monitored for safety and effectiveness after treatment, including hospital discharge and 3-month assessments

3 months

Multiple visits (in-person and virtual)

Long-term Follow-up

Participants are monitored for long-term safety and effectiveness, with assessments at 12, 18, and 24 months post-surgery

24 months

Periodic visits (in-person and virtual)

Treatment Details

Interventions

• Autologous Mononuclear Cells

Trial Overview The study tests the effects of injecting autologous mononuclear cells directly into the heart muscle during Fontan surgery on kids with single right ventricle defects. It aims to see if this treatment improves heart structure and function compared to those not receiving stem cells.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

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.

Group II: Control Arm Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Timothy J Nelson, MD, PhD

Lead Sponsor

Trials

5

Recruited

170+

Children's of Alabama

Collaborator

Trials

10

Recruited

3,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Children's Hospitals and Clinics of Minnesota

Collaborator

Trials

67

Recruited

5,022,000+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Ochsner Health System

Collaborator

Trials

97

Recruited

91,900+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Findings from Research

The study successfully demonstrated the feasibility and safety of transplanting autologous umbilical cord blood mononuclear cells (UCB-MNCs) into the right ventricle of juvenile porcine hearts, with no mortalities and minimal complications observed over a 3-month monitoring period.

The results indicate that UCB-MNCs can be safely delivered in a pediatric setting, providing a promising foundation for future clinical trials aimed at using cell-based therapies for congenital heart diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility for pediatric cardiac regeneration using epicardial delivery of autologous umbilical cord blood-derived mononuclear cells established in a porcine model system. Cantero Peral, S., Burkhart, HM., Oommen, S., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stem cells for repair of the heart. [2007]

2. United States pubmed.ncbi.nlm.nih.gov

Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Intracoronary bone marrow cell application for terminal heart failure in children. [2012]

4. Chile pubmed.ncbi.nlm.nih.gov

[Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy]. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

A regenerative strategy for heart failure in hypoplastic left heart syndrome: intracoronary administration of autologous bone marrow-derived progenitor cells. [2012]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiac Progenitor Cells Enhance Neonatal Right Ventricular Function After Pulmonary Artery Banding. [2017]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Cell therapy of chronic heart failure: State of the art]. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and feasibility for pediatric cardiac regeneration using epicardial delivery of autologous umbilical cord blood-derived mononuclear cells established in a porcine model system. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Allogeneic Mesenchymal Stromal Cell Injection to Alleviate Ischemic Heart Failure Following Arterial Switch Operation. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cell-Based Therapy for Myocardial Dysfunction After Fontan Operation in Hypoplastic Left Heart Syndrome. [2020]