Stem Cell Therapy for Hypoplastic Left Heart Syndrome

Recruiting at 7 trial locations

Overseen By Lynn Padley

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Timothy J Nelson, MD, PhD

Disqualifiers: Severe chronic diseases, Cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: One-time treatment during Stage II surgery

95 Participants Needed

Trial Summary

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 Umbilical Cord Blood Derived Mononuclear Cells for Hypoplastic Left Heart Syndrome?

Research shows that using umbilical cord blood cells in patients with Hypoplastic Left Heart Syndrome can help maintain heart function after surgery, as seen in a study where patients receiving the treatment had stable heart function compared to those who did not. Additionally, similar treatments using stem cells have shown promise in improving heart function in animal models and other heart conditions. ^{1 2 3 4 5}

Is stem cell therapy safe for humans with hypoplastic left heart syndrome?

Research shows that using autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) in patients with hypoplastic left heart syndrome (HLHS) has been generally safe. In a study with infants undergoing heart surgery, no serious safety issues were reported, and the therapy did not cause any harmful effects. ^{1 6 7 8 9}

How does stem cell therapy differ from other treatments for hypoplastic left heart syndrome?

Stem cell therapy for hypoplastic left heart syndrome is unique because it involves using the patient's own cells, specifically umbilical cord blood-derived mononuclear cells, to potentially improve heart function. This approach is different from traditional treatments as it aims to regenerate heart tissue and improve right ventricle function, which is crucial for patients with this condition. ^{1 2 4 6 9}

What is the purpose of this trial?

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.

Research Team

Joseph W Rossano, M.D.

Principal Investigator

Children's Hospital of Philadelphia

Waldemar A Carlo, MD

Principal Investigator

University of Alabama at Birmingham

Harold M Burkhart, M.D.

Principal Investigator

Children's Hospital Oklahoma University Medical Center

David M Overman, M.D.

Principal Investigator

Children's Minnesota

Ram Kumar Subramanyan, M.D.

Principal Investigator

Children's Hospital Los Angeles

Benjamin Peeler, M.D.

Principal Investigator

Ochsner Health System

James Tweddell, M.D.

Principal Investigator

Children's Hospital Medical Center, Cincinnati

James Jaggers, M.D.

Principal Investigator

Children's Hospital Colorado

Frank Cetta, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for children under 13 months old with Hypoplastic Left Heart Syndrome or a similar condition, who've had Stage I surgery and are set for Stage II. They must have their own umbilical cord blood cells available for treatment. Kids with severe chronic diseases, pulmonary hypertension, recent urgent procedures without recovery, cancer history, or syndromic features can't participate.

Inclusion Criteria

You have previously participated in a UCB collection protocol and used your own UCB-MNC product for treatment.

I was younger than 13 months when I had my Stage II surgery.

I have HLHS or a similar condition and am between my first and second heart surgeries.

Exclusion Criteria

I have a history of cancer.

My medical records show I have severe pulmonary hypertension.

You have other symptoms outside of the heart that are part of a specific condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intramyocardial injection of autologous umbilical cord blood derived mononuclear cells during Stage II surgical repair

One-time treatment during Stage II surgery

1 visit (in-person)

Follow-up

Participants are monitored for changes in cardiac function and other health metrics post-treatment

12 months

Regular follow-up visits including imaging studies at 3 months and 12 months post-surgery

Long-term Follow-up

Monitoring for long-term outcomes such as eligibility for Stage III surgical repair and time to cardiac transplantation

Up to 4 years

Treatment Details

Interventions

• Autologous Umbilical Cord Blood Derived Mononuclear Cells

Trial Overview The study tests injecting autologous (self-donated) mononuclear cells from umbilical cord blood into the heart muscle during Stage II surgery in kids with certain heart conditions. It aims to see if this stem cell therapy improves heart structure/function compared to those without such treatment.

Participant Groups

Group I: Treatment Experimental Treatment 2 Interventions

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 .

Group II: Control Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Timothy J Nelson, MD, PhD

Lead Sponsor

Trials

5

Recruited

170+

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 Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Children's Hospitals and Clinics of Minnesota

Collaborator

Trials

67

Recruited

5,022,000+

Ochsner Health System

Collaborator

Trials

97

Recruited

91,900+

Children's of Alabama

Collaborator

Trials

10

Recruited

3,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Findings from Research

In a phase I trial involving 7 patients with Hypoplastic Left Heart Syndrome (HLHS) receiving autologous umbilical cord blood-derived mononuclear cells (UCB-MNC) therapy, the treatment helped preserve right ventricle function after Stage II surgery, with no decrease in fractional area change (FAC) or ejection fraction (EF) compared to a control group.

UCB-MNC therapy also led to significant improvements in weight percentiles over 6 months post-surgery, indicating a potential overall benefit in growth and recovery compared to the control group, which experienced declines in both heart function and weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Impact of Autologous Cell Therapy on Hypoplastic Left Heart Syndrome After Bidirectional Cavopulmonary Anastomosis. Vincenti, M., O'Leary, PW., Qureshi, MY., et al.[2022]

Stem cell therapy shows promise as a novel treatment for managing right ventricular dysfunction in patients with hypoplastic left heart syndrome, a serious congenital heart condition that often leads to significant morbidity after surgical palliation.

Current research indicates that the therapeutic effects of stem cells may primarily result from their paracrine effects—where they release signaling molecules—rather than from direct integration into heart tissue, which is a shift in understanding that could influence future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions. Bittle, GJ., Morales, D., Deatrick, KB., et al.[2020]

The CHILD trial is a Phase I/II study investigating the safety and efficacy of neonatal cardiac-derived progenitor cells (nCPCs) in infants with hypoplastic left heart syndrome (HLHS), aiming to enroll 32 patients across 4 institutions.

Preliminary findings suggest that nCPCs may improve right ventricle function, which is crucial since RV dysfunction is linked to higher mortality in HLHS infants, but the trial is still ongoing to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). Kaushal, S., Hare, JM., Shah, AM., et al.[2022]

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]

Intracoronary delivery of autologous cardiosphere-derived cells (CDCs) in 14 children with hypoplastic left heart syndrome was found to be feasible and safe, with no serious adverse events reported during an 18-month follow-up.

Patients receiving CDCs showed significant improvements in right ventricular ejection fraction and overall cardiac function compared to controls, suggesting potential benefits for long-term clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Ishigami, S., Ohtsuki, S., Tarui, S., et al.[2015]

References

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

Clinical Impact of Autologous Cell Therapy on Hypoplastic Left Heart Syndrome After Bidirectional Cavopulmonary Anastomosis. [2022]

2. 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]

3. China pubmed.ncbi.nlm.nih.gov

[Beneficial effects of human umbilical cord blood mononuclear cells transplantation on rats with experimental myocardial infarction]. [2011]

4. England pubmed.ncbi.nlm.nih.gov

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload. [2018]

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

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions. [2020]

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

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). [2022]

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

Safety and feasibility of adjunct autologous cord blood stem cell therapy during the Norwood heart operation. [2023]

8. 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]

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

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. [2015]