Stem Cell Therapy for Hypoplastic Left Heart Syndrome

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using stem cells from a baby's own umbilical cord blood to improve heart function in children with hypoplastic left heart syndrome (HLHS). The treatment, called Autologous Umbilical Cord Blood Derived Mononuclear Cells, is administered during routine heart surgery. Researchers will compare the results with those of children who do not receive the stem cells. This study may suit babies under 13 months old with HLHS who are scheduled for this specific heart surgery. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using a person's own umbilical cord blood cells has been tested in earlier studies. These studies found that injecting these cells into the heart muscle is generally safe. For example, research indicates that these injections were well-tolerated in babies with heart conditions like hypoplastic left heart syndrome.

Additionally, patients who received similar stem cell treatments did not experience major side effects. The cells were injected during heart surgery, and this procedure proved feasible without serious problems. This suggests that using a patient's own stem cells from their umbilical cord blood might be a safe option for treating certain heart conditions. However, discussing any concerns with healthcare providers before deciding to join a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypoplastic left heart syndrome?

Unlike the standard treatments for Hypoplastic Left Heart Syndrome, which typically involve multiple complex surgeries, this new approach utilizes autologous umbilical cord blood-derived mononuclear cells. Researchers are excited about this treatment because it involves injecting a patient's own cells directly into the heart muscle during surgery, potentially enhancing heart repair and function. This method not only targets the condition at a cellular level but also leverages the body's natural healing processes, offering a promising alternative to existing surgical options.

What evidence suggests that this stem cell therapy might be an effective treatment for hypoplastic left heart syndrome?

Research has shown that using a child's own umbilical cord blood cells might help treat hypoplastic left heart syndrome (HLHS). In this trial, some participants will receive autologous umbilical cord blood-derived mononuclear cells injected into the surface of the right heart muscle during their Stage II heart surgery. Earlier studies demonstrated that these stem cells helped maintain the function of the right side of the heart. Specifically, children who received this treatment showed improved heart function and reached important growth and development milestones. Overall, the treatment appears to support better heart health in children with HLHS. ^{1 2 3 6 7}

Who Is on the 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

James Tweddell, M.D.

Principal Investigator

Children's Hospital Medical Center, Cincinnati

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 Jaggers, M.D.

Principal Investigator

Children's Hospital Colorado

Frank Cetta, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12044795/

Autologous umbilical cord blood mononuclear cell therapy ... Preliminary phase I clinical trial results revealed that autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) preserved right ventricular ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40312733/

Autologous umbilical cord blood mononuclear cell therapy ... Autologous umbilical cord blood mononuclear cell therapy for hypoplastic left heart syndrome: a nonrandomized control trial of the efficacy and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03779711

Study Details | NCT03779711 | Intramyocardial Injection of ... Long-term improvement in cardiac function, reaching growth and developmental milestones, reaching Stage III surgical repair pre-op work-up, prolonging time to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022522319311547

Autologous stem cell therapy for hypoplastic left heart ... Results. All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01883076

Safety Study of Autologous Umbilical Cord Blood Cells for ... This study is a Phase I trial to determine the safety of autologous mononuclear cells (MNC) derived from umbilical cord blood for intramyocardial delivery into ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20112829

A Study of Autologous Umbilical Cord Blood Derived ... This is a Phase I study to determine the safety and feasibility of injections of autologous umbilical cord blood (UCB) cells into the right ventricle of ...

7. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00528-0/fulltext

Feasibility and safety of autologous cord blood derived cell ... Early phase clinical trials have administered autologous UCB-derived cell therapy safely to term neonates with birth asphyxia and hypoplastic ...