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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using mesenchymal stem cells to aid those with dilated cardiomyopathy (heart muscle weakness). Researchers aim to determine if this treatment is safe and effective in improving heart function. Participants will be divided into groups, with some receiving the stem cell therapy (Allogeneic Human Mesenchymal Stem Cells, or hMSCs) and others a placebo. Individuals with non-ischemic dilated cardiomyopathy who have been on stable heart medications for at least 30 days may find this trial suitable. 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using certain types of stem cells from donors, called allogeneic human mesenchymal stem cells (hMSCs), appears safe for people. In past studies, these stem cells have been given to patients with various health issues, such as heart problems. One study found that these stem cells improved heart function without major safety concerns. Another study tested similar stem cells injected into joints and found they were generally well-tolerated, with no serious side effects.

These results suggest the treatment is relatively safe, but it's important to remember that this trial remains in the early stages. Researchers are still learning about how well the treatment works for different people. Always consult a healthcare provider to understand personal risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dilated cardiomyopathy?

Most treatments for dilated cardiomyopathy, like beta-blockers, ACE inhibitors, and implantable devices, focus on managing symptoms and preventing complications. But allogeneic human mesenchymal stem cells (hMSCs) offer a novel approach by potentially regenerating damaged heart tissue. These stem cells can differentiate into various cell types and release factors that encourage tissue repair and reduce inflammation. Researchers are excited because this regenerative capability could directly address the underlying heart muscle damage, potentially improving heart function in ways current treatments can't.

What evidence suggests that this trial's treatments could be effective for dilated cardiomyopathy?

Research has shown that certain donor stem cells, known as allogeneic human mesenchymal stem cells (hMSCs), can improve heart function in individuals with dilated cardiomyopathy. In this trial, some participants will receive hMSC therapy, while others will receive a placebo. Animal studies have found that these stem cells can reduce harmful changes in the heart, a major issue in this condition. In some human trials, patients who received stem cell therapy experienced improved heart function and overall heart health. This therapy works by reducing inflammation and aiding the repair of damaged heart tissue. Although more research is needed to confirm these benefits in larger groups, early results are promising. ^{1 3 5 6 7}

Who Is on the Research Team?

Joshua Hare, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 eligible for a heart catheterization procedure.

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

My heart pumps less blood than normal.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04208646

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2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7762005/

Efficacy and Mode of Action of Mesenchymal Stem Cells in ... Adipose Tissue-Derived Mesenchymal * Adipose Tissue Derived ... derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

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Stem Cell Treatment for Dilated Cardiomyopathy: A Review of ... The progression of cardiomyopathy to more serious outcomes, such as heart failure, is largely due to adverse cardiac remodeling and the limited ...

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05816-1

a phase I clinical trial | Journal of Translational Medicine Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model. Regen Ther. 2021;18:182–90.

5. ahajournals.org ahajournals.org/doi/10.1161/circresaha.117.311827

Dose Comparison Study of Allogeneic Mesenchymal Stem ... ... derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy. ... Adipose Tissue-Derived Stem Cells.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32677876/

Intra-articular injections of allogeneic human adipose ... Aim: This study investigated the safety and clinical outcomes of expanded allogeneic human adipose-derived mesenchymal progenitor cells injected into patients ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2352396415000870

Allogeneic Mesenchymal Stem Cells Restore Endothelial ... Original Article. Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells.