Umbilical Cord Blood Therapy for Hypoplastic Left Heart Syndrome

No longer recruiting at 1 trial location

Overseen By Karen S Miller

Age: Any Age

Sex: Female

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Unwilling to participate

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of umbilical cord blood to repair heart defects in newborns with hypoplastic left heart syndrome. The researchers will collect and process cells from the cord blood to determine their potential for future heart repair treatments. Pregnant women informed that their baby has this heart condition can participate by agreeing to store the umbilical cord blood for research. This could lead to new treatments for babies with heart defects. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that may result in innovative treatments for newborns with heart defects.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that umbilical cord blood collection and processing is safe for cardiac repair?

Research has shown that using cells from a newborn's umbilical cord to repair the heart is generally safe. Studies have found that these cells do not cause serious side effects. For instance, early trials safely used these cells in newborns with heart problems, such as hypoplastic left heart syndrome. Researchers discovered that patients tolerated the cells well, experiencing no major health issues from the treatment.

These findings suggest that using a baby's own cells might help fix heart problems without causing harm. However, continued study of these treatments is important to ensure their long-term safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about umbilical cord blood therapy for Hypoplastic Left Heart Syndrome (HLHS) because it uses the patient's own stem cells, potentially reducing the risk of rejection. Unlike current treatments, such as multiple surgeries or heart transplants, this approach aims to utilize autologous stem cells derived from the baby's umbilical cord blood to promote heart tissue repair and regeneration. This novel method could offer a more natural and less invasive option to support heart function and improve outcomes for babies with HLHS.

What evidence suggests that umbilical cord blood therapy might be an effective treatment for hypoplastic left heart syndrome?

Research has shown that stem cells from umbilical cord blood can repair heart damage. Studies have found these cells effectively heal and renew injured heart tissue. In this trial, researchers collect umbilical cord blood from newborns diagnosed with hypoplastic left heart syndrome. Early trials suggested that using a patient's own cord blood cells might improve heart function over time. Additionally, evidence indicates these cells can help young patients grow and reach developmental milestones more effectively. Overall, using umbilical cord blood cells appears promising for repairing heart issues in congenital heart conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Susana Cantero Peral, MD PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for parents of babies diagnosed prenatally with hypoplastic left heart syndrome, who are willing to have their baby's umbilical cord blood collected and stored for research on cardiac repair. Parents must agree to follow-up questions about the baby's health status.

Inclusion Criteria

One or both parents willing to consent to the storage of umbilical cord blood for regenerative research

Delivering party and/or expectant family willing to sign Release of Information to request fetal echo text report diagnosing severe CHD/hypoplastic left heart syndrome

Parent(s) willing to be contacted 60 days after collection for follow-up screening questions regarding the health status of the baby affected with severe CHD/hypoplastic left heart syndrome

Exclusion Criteria

I am willing to participate in the clinical trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Umbilical Cord Blood Collection

Umbilical Cord Blood is drawn from the umbilical cord of newborn babies diagnosed with Hypoplastic Left Heart Syndrome, before placental detachment.

At birth

1 visit (in-person)

Processing and Storage

Cord blood is processed to produce a stem cell product and then frozen for potential future use.

Immediate processing

Follow-up

Participants are monitored for safety and effectiveness after treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Umbilical Cord Blood Collection and Processing

Trial Overview The study tests the collection, processing, and storage of umbilical cord blood from newborns with hypoplastic left heart syndrome. The goal is to see if these cells can be used in future therapies aimed at repairing congenital heart defects.

How Is the Trial Designed?

Group I: Umbilical Cord Blood Collection Experimental Treatment 1 Intervention

Umbilical Cord Blood is drawn from the umbilical cord of newborn babies diagnosed with Hypoplastic Left Heart Syndrome, before placental detachment. Cord blood is packaged in a Credo Cube, and sent at a temperate state to the manufacturer immediately after draw. At least 65 mL of cord blood is needed to produce a stem cell product during manufacturing. Once processed, the patient's autologous cord blood stem cells will be frozen for their potential future use in a clinical trial.

Umbilical Cord Blood Collection and Processing is already approved in United States, European Union for the following indications:

Approved in United States as Umbilical Cord Blood for:

• Hematopoietic cell transplantation
• Congenital heart diseases
• Neurodegenerative diseases
• Cerebral palsy
• Diabetes and its complications

Approved in European Union as Umbilical Cord Blood for:

• Hematopoietic cell transplantation
• Congenital heart diseases
• Neurodegenerative diseases
• Cerebral palsy
• Diabetes and its complications

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

The endothelium-targeted soluble Notch ligand (hD1R) significantly increased the number of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood during ex vivo expansion, enhancing their potential for transplantation.

In vivo studies showed that hD1R not only promoted the regeneration of donor cells in recipient mice but also accelerated hematopoietic recovery, especially when the initial dose of HSPCs was low, suggesting its potential to improve outcomes in umbilical cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelium-targeted human Delta-like 1 enhances the regeneration and homing of human cord blood stem and progenitor cells. Tian, DM., Liang, YM., Zhang, YQ.[2019]

Human umbilical cord blood-derived stem cells (UCBSCs) can be effectively isolated and expanded, showing a duplication time of approximately 2.16 days, making them a promising alternative source for cardiac cell-based therapies.

UCBSCs express key proteins important for heart regeneration, such as connexin-43 and SERCA-2, but do not express cardiac-specific transcription factors or sarcomeric proteins, indicating their potential for myocardial-cell replacement while still requiring further differentiation to achieve full cardiac functionality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood-derived stem cells spontaneously express cardiomyogenic traits. Prat-Vidal, C., Roura, S., Farré, J., et al.[2007]

In a study involving 38 extremely preterm infants (born at less than 28 weeks), umbilical cord blood (UCB) collection for autologous use was feasible, with 71% of infants providing enough volume for cryopreservation and 73.6% yielding sufficient total nucleated cells (TNCs).

The UCB from extremely preterm infants showed a higher CD34+ to TNC ratio compared to full-term values, suggesting potential for effective treatment in neonatal brain injury, with ongoing research to assess the safety of UCB cell administration in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants. Zhou, L., McDonald, CA., Yawno, T., et al.[2023]

Umbilical cord blood is a valuable source of hematopoietic stem cells for treating hematological diseases, with significant advancements in its use for pediatric patients since the first successful transplantation in a child with Fanconi anemia.

Recent improvements in transplantation techniques have expanded the successful application of umbilical cord blood transplantation to adult patients, enhancing treatment outcomes for a wider range of hematological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New techniques for umbilical cord blood transplantation]. Zhang, Y.[2018]

Over an 8-year period, 1256 umbilical cord blood (UCB) units were collected in northeast Mexico, with only 34% being banked due to low volume or low total nucleated cell (TNC) counts, highlighting challenges in collection quality.

The cryopreserved UCB units demonstrated high cell viability (99.3%) and a median CD34+ cell content of 4.0×10^6, indicating that while the utilization rate for transplantation was low (3.7%), the quality of the banked units was generally good.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood banking activities at a university hospital in northeast Mexico: an 8-year experience. Jaime-Perez, JC., Monreal-Robles, R., Colunga-Pedraza, J., et al.[2023]

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]

Collecting umbilical cord blood (UCB) from preterm infants after delayed cord clamping is both feasible and safe, with no significant increase in complications compared to those without collection.

The number of mononuclear cells (MNCs) obtained from preterm infants meets the necessary criteria for potential therapeutic use, suggesting that UCB from preterm infants should be reconsidered as a valuable source for stem cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of umbilical cord blood collection from preterm neonates after delayed cord clamping for the use of improving preterm complications. Ren, Z., Xu, F., Wang, J., et al.[2021]

In a study of 285 maternal-neonatal donor pairs, only 44% were eligible to donate umbilical cord blood (UCB) due to various maternal health issues, highlighting challenges in sourcing safe UCB for transplantation.

Common reasons for ineligibility included maternal fever at delivery, chronic diseases, and histories of sexually transmitted diseases, indicating the need for refined donor criteria to improve eligibility rates, especially in high-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High deferral rate for maternal-neonatal donor pairs for an allogeneic umbilical cord blood bank. Jefferies, LC., Albertus, M., Morgan, MA., et al.[2019]

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]

Umbilical cord blood is a promising source of hematopoietic stem cells for treating hematologic diseases, showing high success rates in pediatric patients and improving outcomes for adults through better matching and cell doses.

Recent advancements, such as the use of double umbilical cord blood units and enhanced supportive care, have led to faster engraftment times and ongoing comparisons with other graft sources in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation: the first 25 years and beyond. Ballen, KK., Gluckman, E., Broxmeyer, HE.[2022]

Citations

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

Autologous umbilical cord blood mononuclear cell therapy ... The use of stem cells is effective in regenerating, remodeling, and renewing injured myocardium. Although preliminary clinical trials reported ...

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/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 ...

4. 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 ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20450452

Clinical Trials The purpose of this study is to determine the safety and feasibility of injections of autologous umbilical cord blood (UCB) cells into the right ventricle of ...

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 ...