Stem Cell Therapy for Dilated Cardiomyopathy

(DCMII Trial)

Recruiting at 2 trial locations

Overseen By Roberto Bolli, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joshua M Hare

Must be taking: Beta blockers, ACE inhibitors

Disqualifiers: Coronary artery disease, Valvular heart disease, Liver dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

136 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called human allogeneic mesenchymal stem cell therapy.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable regimen of certain heart medications, like beta blockers and ACE inhibitors, for at least 30 days before the procedure. If you're already taking these medications, you won't need to stop them, but you should discuss any other medications with the trial team.

What data supports the effectiveness of the treatment Allogeneic Human Mesenchymal Stem Cells (hMSCs) for Dilated Cardiomyopathy?

Research shows that mesenchymal stem cells (MSCs) can help repair damaged heart tissue by reducing inflammation and promoting new blood vessel growth. Studies have demonstrated their potential to improve heart function in conditions similar to dilated cardiomyopathy. ^{1 2 3 4 5}

Is stem cell therapy safe for humans?

Safety of allogeneic mesenchymal stem cells (hMSCs) has been established in Phase I and II trials, showing they are generally safe in humans, although specific data for dilated cardiomyopathy is limited. ^{1 2 6 7 8}

How is the stem cell treatment for dilated cardiomyopathy different from other treatments?

This treatment uses allogeneic human mesenchymal stem cells (hMSCs) which are derived from donors, making it less invasive than treatments requiring the patient's own cells. It is administered intravenously, which avoids the need for cardiac catheterization, and it has shown potential to reduce inflammation and improve heart function in dilated cardiomyopathy. ^{1 2 4 5 6}

Research Team

Joshua Hare, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults aged 18-80 with non-ischemic dilated cardiomyopathy (NIDCM) and a left ventricular ejection fraction ≤45%. Participants must be on stable heart medication for at least 30 days. Exclusions include drug/alcohol abuse, certain types of cardiomyopathy, recent organ/cell transplant rejection, coronary artery disease history, known LV thrombus or aneurysm, severe allergies to specific antibiotics or DMSO.

Inclusion Criteria

I am between 18 and 80 years old.

I am eligible for a heart catheterization procedure.

I am on a stable heart medication regimen for non-ischemic cardiomyopathy.

Exclusion Criteria

I have had a transplant rejection in the past.

You have had problems with drugs or alcohol in the past 9 months.

I need a procedure to improve blood flow to my heart.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the experimental human allogeneic mesenchymal stem cell therapy or placebo based on their genotype group

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cardiac function and exercise tolerance

12 months

Treatment Details

Interventions

• Allogeneic Human Mesenchymal Stem Cells (hMSCs)
• Placebo

Trial Overview The study tests the safety and effectiveness of allogeneic human mesenchymal stem cells (hMSCs) versus placebo in treating NIDCM. Patients will receive either hMSCs or placebo through transendocardial injection during cardiac catheterization.

Participant Groups

Group I: Genotype C administered with hMSC Group Experimental Treatment 1 Intervention

Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the treatment group will receive the hMSC intervention.

Group II: Genotype B administered with hMSC Group Experimental Treatment 1 Intervention

Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the treatment group will receive the hMSC intervention.

Group III: Genotype A administered with hMSC Group Experimental Treatment 1 Intervention

Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the treatment group will receive the hMSC intervention.

Group IV: Genotype A administered with placebo Group Placebo Group 1 Intervention

Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the placebo group will receive the placebo intervention.

Group V: Genotype C administered with placebo Group Placebo Group 1 Intervention

Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the placebo group will receive the placebo intervention.

Group VI: Genotype B administered with placebo Group Placebo Group 1 Intervention

Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the placebo group will receive the placebo intervention.

Allogeneic Human Mesenchymal Stem Cells (hMSCs) is already approved in European Union, Japan, India for the following indications:

Approved in European Union as Alofisel for:

• Complex perianal fistulas in patients with Crohn’s disease

Approved in Japan as Stemirac for:

• Treatment of spinal cord injury

Approved in India as Stempeucel for:

• Critical Limb Ischemia

Approved in Japan as TEMCELL for:

• Acute graft-versus-host disease

Who Is Running the Clinical Trial?

Joshua M Hare

Lead Sponsor

Trials

17

Recruited

430+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Findings from Research

Intravenous administration of allogeneic placental matrix-derived mesenchymal stem cells shows promise for treating dilated cardiomyopathy, with preclinical studies indicating benefits such as reduced inflammation and improved blood vessel formation.

A case report highlights significant clinical improvement in a patient with dilated cardiomyopathy after treatment with these stem cells, suggesting a potential new approach for this condition that avoids the invasiveness of traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy. Ichim, TE., Solano, F., Brenes, R., et al.[2019]

In a study involving 37 patients with chronic nonischemic dilated cardiomyopathy, allogeneic (allo) bone marrow-derived human mesenchymal stem cells (hMSCs) showed a significant increase in ejection fraction by 8.0 percentage points compared to 5.4 percentage points with autologous (auto) hMSCs, indicating better efficacy of allo-hMSCs in improving heart function.

The allo-hMSC group also demonstrated a lower rate of major adverse cardiac events and a significant improvement in the 6-minute walk test, suggesting that allo-hMSCs may provide a safer and more effective treatment option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. Hare, JM., DiFede, DL., Rieger, AC., et al.[2022]

Mesenchymal stem cells (MSCs) are promising for cardiac repair due to their ability to evade immune recognition and their immune-modulating properties, making them suitable for allogeneic (donor-derived) therapies.

Current preclinical and early clinical studies show that MSC therapy has significant potential to repair damaged cardiac tissue in heart failure patients, highlighting its efficacy in improving heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell therapy for cardiac repair. Boyle, AJ., McNiece, IK., Hare, JM.[2022]

Intracoronary injection of autologous bone marrow-derived mesenchymal stem cells in a child with progressive dilated cardiomyopathy is feasible and safe, suggesting a new therapeutic option for this condition.

The treatment may lead to improvements in the child's functional class, quality of life, and echocardiographic measures of heart function, indicating potential efficacy of stem cell therapy in pediatric dilated cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy. Zeinaloo, A., Zanjani, KS., Bagheri, MM., et al.[2016]

In a study of 53 patients with dilated cardiomyopathy, mesenchymal stem cells (BMSC) showed significant improvements in left ventricular ejection fraction (LVEF), NYHA class, and myocardial perfusion at both 3 and 12 months compared to normal saline, indicating their efficacy in treatment.

Bone marrow mononuclear cells (BMMC) also improved LVEF and NYHA class at 3 months, but did not show sustained benefits at 12 months, suggesting that while both stem cell types are safe, BMSC may be more effective for long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy. Xiao, W., Guo, S., Gao, C., et al.[2017]

In a study involving 30 patients with ischemic cardiomyopathy, both allogeneic and autologous mesenchymal stem cell (MSC) therapies showed low rates of serious adverse events (SAEs) within 30 days, indicating a favorable safety profile for both treatments.

While both types of MSCs improved heart structure by reducing infarct size and LV volumes, only autologous MSCs led to significant improvements in functional capacity and quality of life, as measured by the 6-minute walk test and the Minnesota Living with Heart Failure Questionnaire.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. Hare, JM., Fishman, JE., Gerstenblith, G., et al.[2023]

Intravenous allogeneic human mesenchymal stem cells (hMSCs) were found to be safe for patients after myocardial infarction (MI), with similar rates of adverse events compared to placebo (5.3 vs 7.0 events per patient).

The hMSC treatment showed promising efficacy, including improved ejection fraction and reduced ventricular tachycardia episodes, indicating potential benefits in heart function and recovery after MI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Hare, JM., Traverse, JH., Henry, TD., et al.[2022]

Mesenchymal stem cells (MSCs) show promise in treating myocardial injury, with both autologous and allogeneic transplants demonstrating benefits in preclinical studies and initial clinical experiences, particularly for ischemic cardiomyopathy.

Current research is focused on enhancing the effectiveness of MSC therapy by optimizing the cardiogenic potential of these cells through guided cardiopoiesis, aiming for standardized treatment approaches for heart injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells and cardiac repair: principles and practice. Bartunek, J., Behfar, A., Vanderheyden, M., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy. [2019]

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

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial. [2022]

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

Mesenchymal stem cell therapy for cardiac repair. [2022]

4. Denmark pubmed.ncbi.nlm.nih.gov

Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy. [2016]

5. Japan pubmed.ncbi.nlm.nih.gov

A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy. [2017]

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

Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. [2023]

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

A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. [2022]

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

Mesenchymal stem cells and cardiac repair: principles and practice. [2021]