Stem Cell Therapy for Heart Failure

(HECTOR Trial)

Overseen By Joseph C. Wu, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph C. Wu

Must be taking: Beta-blockers, ACE inhibitors

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Renal failure, Aortic stenosis, Arrhythmia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using stem cells to improve heart function and survival in people with heart failure caused by a past heart attack. Participants will receive varying doses of Human Embryonic Stem Cell-Derived Cardiomyocytes (stem cell-derived heart cells) to determine the most effective dose. This trial suits individuals experiencing heart failure symptoms, such as shortness of breath, with a history of heart attacks affecting their heart's pumping ability. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of certain heart medications, like beta-blockers and ACE inhibitors, for a specific period before joining. If you are on Coumadin, you will need to stop it 5 days before the procedure. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Research shows that treatments using special cells from human embryos, called stem cells, are being tested to help people with heart failure. These stem cells can become heart muscle cells, potentially repairing damaged heart tissue.

Studies have found that these treatments can be safely administered to patients. Evidence indicates that these stem cells can grow and survive in the heart, which is promising for recovery. In one study, the transplanted cells became a small part of the heart tissue after a few weeks, suggesting they integrate well.

While there are no major safety concerns, it's important to note that these are early studies. They primarily focus on assessing the treatment's safety for humans. This means that while the results are positive so far, more research is needed to understand all possible risks and benefits.

For those considering joining a trial, initial research suggests the treatment is well-tolerated and safe. However, individual experiences can vary, and the trial team will provide detailed information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about stem cell therapy for heart failure because it offers a groundbreaking approach by using human embryonic stem cell-derived cardiomyocytes. Unlike traditional treatments like ACE inhibitors, beta-blockers, and diuretics, which mainly manage symptoms and prevent further heart damage, this therapy aims to regenerate damaged heart tissue directly. The study is exploring different doses of stem cells, with low, medium, and high doses (50M, 150M, and 300M cells respectively), to determine the most effective amount for heart repair. This potential for heart tissue regeneration could transform patient outcomes, offering hope for improved heart function and quality of life.

What evidence suggests that Human Embryonic Stem Cell-Derived Cardiomyocytes might be an effective treatment for heart failure?

Research has shown that special heart cells made from human embryonic stem cells (hESC-CMs) could aid in heart repair after a heart attack. In studies, these cells formed new tissue covering about 12% of the damaged heart area just four weeks post-transplantation. This indicates that hESC-CMs can repair heart tissue and might enhance heart function. They have proven more effective in heart repair than other stem cells, such as those from bone marrow. Although further research is necessary, these early results highlight hESC-CMs as a promising treatment for heart failure. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 21-79 with chronic heart failure due to a past heart attack, who can undergo cardiac catheterization and have been on stable heart medication. They must not have severe allergies, organ transplants, life-limiting non-cardiac conditions, significant kidney/liver/blood issues, or be pregnant. Those with recent serious arrhythmias or certain heart devices are excluded.

Inclusion Criteria

My heart's pumping ability is reduced.

I have been on stable heart failure medication for the required time.

I was hospitalized recently or have high NT pro-BNP levels.

Exclusion Criteria

I have a health condition that may limit my life to less than a year.

I have a serious heart rhythm problem without a pacemaker or defibrillator.

I have experienced rejection of a transplanted organ or cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of hESC-CMs to assess safety and establish the maximum tolerated dose

6-8 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac MRI assessments

3 years

Regular follow-up visits for cardiac MRI and safety assessments

What Are the Treatments Tested in This Trial?

Interventions

• Human Embryonic Stem Cell-Derived Cardiomyocyte

Trial Overview The trial is testing three doses (50M, 150M, and 300M cells) of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for improving survival and heart function in patients with chronic left ventricular dysfunction after a myocardial infarction.

How Is the Trial Designed?

Group I: Cohort 2 Active Control 1 Intervention

Medium dose (150M cells)

Group II: Cohort 3 Active Control 1 Intervention

High dose (300M cells)

Group III: Cohort 1 Active Control 1 Intervention

Low dose (50M cells)

Who Is Running the Clinical Trial?

Joseph C. Wu

Lead Sponsor

Trials

3

Recruited

40+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

In a porcine model of heart failure, transplantation of human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) significantly improved heart function compared to human embryonic stem cell-derived cardiomyocytes (hESC-CMs), as indicated by higher left ventricular ejection fraction and other hemodynamic measures after 8 weeks.

hiPSC-MSCs demonstrated a better safety profile than hESC-CMs, with no increase in proarrhythmia or tumor formation, and they enhanced angiogenesis and immune response, contributing to their superior efficacy in improving cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent immunomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure. Liao, S., Zhang, Y., Ting, S., et al.[2020]

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can be used to generate cardiomyocytes, which are heart cells that can potentially be used for cardiac therapies and drug testing, showing robust growth both in lab settings and in living organisms.

Recent studies have shown promising results for using these stem cell-derived cardiomyocytes in repairing heart damage and creating biological pacemakers, but challenges such as ensuring high purity of cardiac cells and preventing immune rejection still need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac applications for human pluripotent stem cells. Shiba, Y., Hauch, KD., Laflamme, MA.[2022]

Human embryonic stem cells (hESCs) have the potential to differentiate into functional cardiomyocytes (hESC-CMs), which can integrate into the heart after transplantation, offering a promising alternative to traditional heart failure treatments.

Current cell-based therapies using adult bone marrow mesenchymal stem cells show favorable outcomes but are limited in their ability to regenerate heart tissue, highlighting the unique advantages of hESC-CMs in addressing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes for heart therapies. Siu, CW., Moore, JC., Li, RA.[2019]

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are emerging as a valuable tool for assessing cardiovascular safety in drug development, allowing for better hazard identification and risk assessment.

A recent User Meeting organized by Pluriomics highlighted the application of Pluricyte® Cardiomyocytes in cardiac safety assessments, emphasizing their role in supporting early decision-making in safety pharmacology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report. Mulder, P., de Korte, T., Dragicevic, E., et al.[2018]

Induced pluripotent stem cell (iPSC) technology allows for the unlimited production of functional human cardiomyocytes, which could potentially treat advanced cardiac failure by supplementing the heart with new cells.

Transplantation of iPSC-derived cardiomyocytes has shown promise in basic studies for improving cardiac function, but further pre-clinical research is needed to assess the safety and efficacy of this therapy before it can be applied in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart. Miyagawa, S., Fukushima, S., Imanishi, Y., et al.[2019]

Transplanting human embryonic stem cell-derived cardiomyocytes (hESC-CMs) into rat hearts after a heart attack significantly improved heart function and reduced heart remodeling, demonstrating their potential for cardiac repair.

In contrast, injecting undifferentiated hESCs led to teratoma formation, while saline and non-cardiomyocyte derivatives resulted in further heart deterioration, highlighting the importance of using pre-differentiated cells for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. Caspi, O., Huber, I., Kehat, I., et al.[2022]

Cellular transplantation has shown promise in preclinical models of heart failure (HF) by improving heart function and promoting repair processes, largely due to the paracrine effects of transplanted stem cells.

Early human studies have yielded modest and inconsistent results, highlighting the need for further research to address challenges and optimize the use of stem cell therapies in managing cardiomyopathy and HF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Therapy for Heart Failure. Psaltis, PJ., Schwarz, N., Toledo-Flores, D., et al.[2019]

Engineered heart muscle (EHM) derived from human embryonic stem cells showed high engraftment rates and long-term survival in a rat model of chronic myocardial infarction, indicating potential for functional benefits in heart repair.

Importantly, the study demonstrated safety, as no teratomas or tumors were observed in any of the animals monitored, suggesting that EHM transplantation does not pose significant risks of tumor formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. Riegler, J., Tiburcy, M., Ebert, A., et al.[2022]

Human embryonic stem cells (hESCs) can be differentiated into cardiomyocytes (hESC-CMs), which possess cardiac-type action potentials and contractile properties, making them valuable for drug discovery and regenerative medicine.

Using hESC-CMs in in vitro assays can improve the predictive value of cardiac safety pharmacology tests, particularly in assessing the risk of proarrhythmic side effects, such as QT prolongation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. He, JQ., January, CT., Thomson, JA., et al.[2022]

Cardiac stem cell therapy using bone-marrow-derived stem cells shows promise for heart regeneration after heart attacks or in heart failure, and initial clinical data suggest it is safe with no increase in adverse events.

However, the confidence in safety is limited due to the small number of patients treated and lack of long-term follow-up, highlighting the need for more extensive data from ongoing and future trials to address potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? Bartunek, J., Vanderheyden, M., Wijns, W., et al.[2007]

The loss of functional heart cells (cardiomyocytes) leads to heart failure, and current treatments are limited since adult hearts cannot regenerate these cells.

This review explores the potential of using human embryonic stem cell-derived cardiomyocytes and vascular cells as a promising therapy for repairing heart tissue damaged by myocardial infarction and treating end-stage heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiovascular repair. Nir, SG., David, R., Zaruba, M., et al.[2019]

Human embryonic stem cells (hESC) can be differentiated into cardiomyocytes, offering a promising source for myocardial cell replacement strategies in heart failure treatment.

The review highlights the structural and functional properties of hESC-derived cardiomyocytes and discusses the challenges and necessary steps for translating this technology into clinical applications for cardiac therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human embryonic stem cells for cardiomyogenesis. Habib, M., Caspi, O., Gepstein, L.[2008]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12109878/

Cardiac Repair and Clinical Outcomes of Stem Cell ... Conclusion: While MSC therapy was safe and improved QoL for HFrEF patients, it did not significantly improve LVEF or other efficacy outcomes.

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCRESAHA.119.314869

Human Embryonic Stem Cell–Derived Cardiomyocytes At 4 weeks after transplantation, grafts averaged ≈12% of infarct size. The authors conclude that that their data “demonstrate that ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4649260/

Comparison of Human Embryonic Stem Cell-Derived ... hESC-CMs and CVPs show similar efficacy for cardiac repair, and both are more efficient than hBM-MNCs. However, hESC-CVPs do not form larger grafts.

4. cirm.ca.gov cirm.ca.gov/our-progress/awards/human-embryonic-stem-cell-derived-cardiomyocytes-patients-end-stage-heart-failure-2/

Human Embryonic Stem Cell-Derived Cardiomyocytes for ... Patients with end-stage heart failure have a 2-year survival rate of only 50% with conventional medical therapy. This dismal survival rate is actually ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05068674

NCT05068674 | Human Embryonic Stem Cell-Derived ... This clinical study will utilize a new cell therapy approach (Human embryonic stem cells derived cardiomyocytes or hESC-CMs) to improve survival and cardiac ...

6. cirm.ca.gov cirm.ca.gov/our-progress/awards/human-embryonic-stem-cell-derived-cardiomyocytes-patients-end-stage-heart-failure/

Human Embryonic Stem Cell-Derived Cardiomyocytes for ... Patients with end-stage heart failure (ESHF) have a 2-year survival rate of 50% with conventional medical therapy. This dismal survival rate is actually ...

7. jacc.org jacc.org/doi/10.1016/j.jacbts.2025.01.007

Reviving Hearts, Restoring Lives: Long-Term Outcomes of ... In summary, the current first-in-human study of allogeneic iPSC-derived cardiomyocyte transplantation provides the longest safety data in ...