Stem Cell Therapy for Heart Failure
(HECTOR Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
Trial Summary
What is the purpose of this trial?This clinical study will utilize a new cell therapy approach (Human embryonic stem cells derived cardiomyocytes or hESC-CMs) to improve survival and cardiac function in patients with chronic left ventricular dysfunction secondary to MI (Myocardial Infarction).
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.
What data supports the effectiveness of the treatment Human Embryonic Stem Cell-Derived Cardiomyocytes for heart failure?
Research shows that human embryonic stem cell-derived cardiomyocytes can improve heart function by replacing damaged heart cells and supporting heart repair processes. Studies in animal models have demonstrated their potential to survive long-term and prevent heart failure progression, offering hope for their use in treating heart conditions.
12345Is stem cell therapy for heart failure safe?
The safety of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for heart failure is still being studied, with some research focusing on potential side effects like arrhythmias (irregular heartbeats). While early studies in animals show promise, more research is needed to confirm safety in humans.
16789How is the treatment using human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for heart failure different from other treatments?
This treatment is unique because it uses human embryonic stem cells to create new heart cells that can integrate with the patient's heart, potentially repairing damaged tissue, unlike traditional treatments that rely on medication or mechanical devices.
15101112Eligibility Criteria
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.
+6 more
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.
+18 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Active Control
Group I: Cohort 2Active Control1 Intervention
Medium dose (150M cells)
Group II: Cohort 3Active Control1 Intervention
High dose (300M cells)
Group III: Cohort 1Active Control1 Intervention
Low dose (50M cells)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford Hospital and ClinicsPalo Alto, CA
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Who Is Running the Clinical Trial?
Joseph C. WuLead Sponsor
California Institute for Regenerative Medicine (CIRM)Collaborator
References
Potent immunomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure. [2020]Optimal cell type as cell-based therapies for heart failure (HF) remains unclear. We sought to compare the safety and efficacy of direct intramyocardial transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) in a porcine model of HF.
Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. [2022]Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure.
Human embryonic stem cells for cardiomyogenesis. [2008]Myocardial cell replacement strategies are emerging as novel therapeutic paradigms for heart failure but are hampered by the paucity of sources for human cardiomyocytes. Human embryonic stem cells (hESC) are pluripotent stem cell lines derived from human blastocysts that can be propagated, in culture, in the undifferentiated state under special conditions and coaxed to differentiate into cell derivatives of all three germ layers, including cardiomyocytes. The current review describes the derivation and properties of the hESC lines and the different cardiomyocyte differentiation system established so far using these cells. Data regarding the structural, molecular, and functional properties of the hESC-derived cardiomyocytes is provided as well as description of the methods used to achieve cardiomyocyte enrichment and purification in this system. The possible applications of this unique differentiation system in several cardiovascular research and applied areas are discussed. Specific emphasis is put on the descriptions of the efforts performed to date to assess the feasibility of this emerging technology in the fields of cardiac cell replacement therapy and tissue engineering. Finally, the obstacles remaining on the road to clinical translation are described as well as the steps required to fully harness the potential of this new technology.
Cellular Therapy for Heart Failure. [2019]The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management.
Cardiac applications for human pluripotent stem cells. [2022]Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyocytes of potential use in cell-based cardiac therapies, high-throughput screening and safety testing of new drugs, and modeling human heart development. These stem cell-derived cardiomyocytes have an unambiguous cardiac phenotype and proliferate robustly both in vitro and in vivo. Recent transplantation studies in preclinical models have provided exciting proof-of-principle for their use in infarct repair and in the formation of a "biological pacemaker". While these successes give reason for cautious optimism, major challenges remain to the successful application of hESCs (or hiPSCs) to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. In this review, we describe the phenotype of hESC- and hiPSC-derived cardiomyocytes, the state of preclinical transplantation studies with these cells, and potential approaches to overcome the aforementioned hurdles.
Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. [2022]Human embryonic stem cells (hESCs) can provide potentially unlimited quantities of a wide range of human cell types that can be used in drug discovery and development, basic research and regenerative medicine. In this review, the authors describe the differentiation of hESCs into cardiomyocytes and outline the properties of hESC-derived cardiomyocytes (hESC-CMs), including their cardiac-type action potentials and contractile characteristics. In vitro cellular assays using hESC-CMs, which can be genetically engineered to create target-specific reporters as well as human disease models, will have applications at multiple stages of the drug discovery process. Furthermore, cardiac safety pharmacology assays evaluating the risk of proarrhythmic side effects associated with QT prolongation may be enhanced in their predictive value with the use of hESC-CMs.
Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report. [2018]Safety pharmacology studies that evaluate drug candidates for potential cardiovascular liabilities remain a critical component of drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have recently emerged as a new and promising tool for preclinical hazard identification and risk assessment of drugs. Recently, Pluriomics organized its first User Meeting entitled 'Combining Pluricyte® Cardiomyocytes & MEA for Safety Pharmacology applications', consisting of scientific sessions and live demonstrations, which provided the opportunity to discuss the application of hiPSC-CMs (Pluricyte® Cardiomyocytes) in cardiac safety assessment to support early decision making in safety pharmacology. This report summarizes the outline and outcome of this Pluriomics User Meeting, which took place on November 24-25, 2016 in Leiden (The Netherlands). To reflect the content of the communications presented at this meeting we have cited key scientific articles and reviews.
Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart. [2019]Advanced cardiac failure is a progressive intractable disease and is the main cause of mortality and morbidity worldwide. Since this pathology is represented by a definite decrease in cardiomyocyte number, supplementation of functional cardiomyocytes into the heart would hypothetically be an ideal therapeutic option. Recently, unlimited in vitro production of human functional cardiomyocytes was established by using induced pluripotent stem cell (iPSC) technology, which avoids the use of human embryos. A number of basic studies including ours have shown that transplantation of iPSCderived cardiomyocytes (iPSC-CMs) into the damaged heart leads to recovery of cardiac function, thereby establishing "proof-of-concept" of this iPSC-transplantation therapy. However, considering clinical application of this therapy, its feasibility, safety, and therapeutic efficacy need to be further investigated in the pre-clinical stage. This review summarizes up-to-date important topics related to safety and efficacy of iPSC-CMs transplantation therapy for cardiac disease and discusses the prospects for this treatment in clinical studies.
Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? [2007]Cardiac stem cell therapy with bone-marrow-derived stem cells is a promising approach to facilitate myocardial regeneration after acute myocardial infarction or in congestive heart failure. The clinical data currently available seem to indicate that this approach is safe and is not associated with an increase in the number of adverse clinical events; nevertheless, the level of safety confidence is limited because of the small number of patients who have been treated and the absence of long-term clinical follow-up data. In order to establish the clinical safety of cardiac stem cell therapy, it will be necessary to collect additional data from both previous and ongoing clinical trials in subsets of patients relative to their background risk. Several conceptual safety concerns should also be addressed. These concerns relate to a number of operational mechanisms and include biological effects on differentiation, remote homing of transplanted stem cells, progression of atherosclerosis, and arrhythmias. The proactive scrutiny of these phenomena could eventually facilitate the translation of the promise of cardiac regeneration into a safe and effective therapy.
Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. [2022]We evaluated the ability of human embryonic stem cells (hESCs) and their cardiomyocyte derivatives (hESC-CMs) to engraft and improve myocardial performance in the rat chronic infarction model.
Human embryonic stem cells for cardiovascular repair. [2019]The critical loss of functional cardiomyocytes causes severe deterioration of pump function, resulting in heart failure. The possibility to regenerate or repair damaged or ischemic cardiac tissue is a great challenge for the future treatment of end-stage heart failure. As cardiomyocytes cannot be regenerated in adults, current therapeutic modalities for the treatment of end-stage heart failure are limited and include medical therapy, mechanical left ventricular assist devices, and cardiac transplantation. This review will focus on the potential use of human embryonic stem (hES) cell-derived cardiomyocytes and vascular cells, as a therapeutic tool for the treatment of myocardial infarction and end-stage heart failure.
Human embryonic stem cell-derived cardiomyocytes for heart therapies. [2019]Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide. Despite substantial improvements in acute management, survivors of myocardial infarction often progress to heart failure. Since adult cardiomyocytes (CMs) do not regenerate, their loss permanently compromises myocardial contractile function. Heart transplantation is currently the last resort for end-stage heart failure, but is hampered by a severe shortage of donor organs and rejection. Cell-based therapies are a promising alternative: Various cell types such as human fetal CMs, skeletal muscle myoblasts and smooth muscle cells have been tested but these approaches are also limited by cell availability or side effects (e.g. due to their non-cardiac identity). In recent years, clinical studies exploiting adult bone marrow mesenchymal stem cells for transplantation in patients with coronary artery disease have reported favorable outcomes but their cardiomyogenic ability is limited. By contrast, human embryonic stem cells (hESCs), derived from the inner cell mass of blastocyst-stage embryos, are pluripotent and can self-renew and differentiate into all cell types including CMs. Furthermore, hESC-derived CMs (hESC-CMs) are viable human heart cells that can functionally integrate with the recipient organ after transplantation. This article reviews the current state and hurdles of hESC-CM research, as well as their therapeutic potentials and limitations.