Neonatal Mesenchymal Cells for Dilated Cardiomyopathy

Recruiting at 4 trial locations

Overseen By William Mahle, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must be taking: Heart failure medications

Must not be taking: Immunosuppressive therapy

Disqualifiers: Heart transplant, Cardiogenic shock, Amyloidosis, others

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

Compensation: Varies

Number of Visits: 6

Duration: 3 months

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on guideline-directed heart failure treatment and cannot be on immune system-altering medications or immunosuppressive therapy at the time of enrollment or within the prior 12 weeks.

What data supports the effectiveness of the treatment Allogeneic Neonatal mesenchymal stromal cells (nMSCs) for dilated cardiomyopathy?

Research shows that mesenchymal stem cells, similar to those in the treatment, can reduce heart inflammation, prevent heart cell death, and improve blood vessel growth in heart disease models. Additionally, a case report showed significant improvement in a patient with dilated cardiomyopathy after receiving similar stem cell therapy. ^{1 2 3 4 5}

Is the treatment with neonatal mesenchymal cells safe for humans?

Studies have shown that using allogeneic mesenchymal stem cells, including those derived from umbilical cords, is generally safe in humans. There were no serious side effects like heart rhythm problems or blood clots reported in trials for dilated cardiomyopathy and other conditions. ^{1 3 4 5 6}

How is the treatment with allogeneic neonatal mesenchymal stromal cells different from other treatments for dilated cardiomyopathy?

This treatment uses neonatal mesenchymal stromal cells, which are younger and potentially more effective than older stem cells, and is administered intravenously, making it less invasive than traditional methods that require bone marrow extraction and cardiac catheterization. ^{1 2 3 4 6}

What is the purpose of this trial?

This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of Dilated Cardiomyopathy. The purpose of the study is to help doctors and scientists learn if allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions are a safe and effective way to improve cardiac function and left ventricular ejection fraction.

Research Team

William Mahle, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for young adults and children with Dilated Cardiomyopathy (DCM), a condition where the heart becomes weakened and enlarged. Participants must meet certain health criteria to be included, but specific inclusion details are not provided here.

Inclusion Criteria

I am between 4 and 17 years old.

I can sign my own consent for the study.

I have been diagnosed with DCM and my heart doesn’t pump well.

Exclusion Criteria

I do not have severe heart valve disease or specific heart muscle conditions.

I have not had recent serious cancer, brain disorders, severe lung clots, high blood pressure, or kidney failure.

I have had heart surgery or treatment for heart defects recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions every 30 days for a total of 3 infusions

3 months

3 visits (in-person) for infusions, plus follow-up visits the morning after each infusion for pediatric patients

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 months, 6 months, and 1 year

12 months

3 visits (in-person) at 3-month, 6-month, and 1-year marks

Treatment Details

Interventions

• Allogeneic Neonatal mesenchymal stromal cells (nMSCs)

Trial Overview The study tests if infusions of allogeneic neonatal mesenchymal stromal cells (nMSCs) can safely improve heart function in patients with DCM. It's an early-stage trial to assess safety and how well the treatment works.

Participant Groups

Group I: Pediatric Cohort Experimental Treatment 1 Intervention

Pediatric participants (ages 4 years-18 years) will be enrolled into dose level as determined in Phase 1B (3+3 study design; open label). nMSCs will be administered intravenously in the following defined dose groups. The rate of infusion will be approximately 30- 60 minutes at 0, 15 and 30 days, with escalating dose levels: * Dose Level 1: 0.7x106 nMSCs/kg * Dose Level 2: 1.43x106 nMSCs/kg * Dose Level 3: 2.85x106 nMSCs/kg Dose escalation will follow 3+3 study design parameters. The next dosing group will be initiated at least one month after the last subject in a particular dose level has received the last dose treatment. Once MTD has been determined, 3 additional patients will be enrolled to ensure a total of 6 patients are enrolled in MTD level for confirmation. Following intravenous delivery of nMSCs, patients will be followed at 3 months, 6 months and 1 year from the last infusion to complete all safety and efficacy assessments.

Group II: Adult Cohort Experimental Treatment 1 Intervention

Adults (18-30 years) will be enrolled into all dose levels (as tolerated) of Phase 1A. Open label nMSCs will be administered intravenously in the following defined dose groups. The rate of infusion will be approximately 30- 60 minutes at 0, 15 and 30 days, with escalating dose levels: * Dose level 1: 5.0x107 nMSCs at 0, 15 and 30 days * Dose level 2: 1.0.x108 nMSCs at 0, 15 and 30 days * Dose level 3: 2.5x108 nMSCs at 0, 15 and 30 days Dose escalation will follow 3+3 study design parameters. The next dosing group will be initiated at least one month after the last subject in a particular dose level has received the last dose treatment. Once MTD has been determined, 3 additional patients will be enrolled to ensure a total of 6 patients are enrolled in MTD level for confirmation.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

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]

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) significantly improved cardiac function in a rat model of dilated cardiomyopathy (DCM), as evidenced by increased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) over a 4-week monitoring period.

hUCMSC treatment not only reduced harmful cardiac biomarkers like BNP and cTNI but also increased beneficial cytokines such as HGF, VEGF, and IGF-1, suggesting that the therapeutic effects may be linked to the regulation of these cytokines and the protection of heart cell structure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. Mao, C., Hou, X., Wang, B., et al.[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 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]

References

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

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

2. China pubmed.ncbi.nlm.nih.gov

[Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with dilated cardiomyopathy]. [2011]

3. England pubmed.ncbi.nlm.nih.gov

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. [2022]

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

Transplantation of allogenic cells in the therapy of patients with dilated cardiomyopathy. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

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

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

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