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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether infusions of neonatal mesenchymal stromal cells (nMSCs) are safe and can improve heart function in individuals with dilated cardiomyopathy, a condition where the heart enlarges and cannot pump blood efficiently. Participants will receive these cell infusions intravenously, with the goal of enhancing heart performance. The trial is open to those with dilated cardiomyopathy who have not responded well to at least three months of standard heart failure treatments. This trial may be suitable for individuals seeking new treatment options. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Research has shown that treatments using special cells from donated umbilical cords are generally safe for patients with dilated cardiomyopathy, a type of heart disease. Studies have found no significant increase in serious heart problems with this therapy, meaning patients did not experience more severe heart issues. Additionally, these stem cell treatments have improved heart function, such as enhancing its ability to pump blood.

However, as this is a Phase 1 study, the primary goal is to assess safety. At this early stage, researchers are still gathering detailed safety information. The Phase 1 status indicates that while the treatment appears promising, its safety is under careful observation. Patients considering joining this trial should be aware that the treatment is still in the early testing stages, and complete safety information is not yet available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for dilated cardiomyopathy, which often include medications like beta-blockers and ACE inhibitors, the investigational treatment using allogeneic neonatal mesenchymal stromal cells (nMSCs) offers a novel approach. Researchers are excited about nMSCs because they harness the regenerative potential of stem cells, which may help repair damaged heart tissue at a cellular level. This treatment is delivered intravenously and could offer a more direct method to enhance heart function and improve patient outcomes. By targeting the root cause of tissue damage, nMSCs have the potential to provide a more effective and long-lasting solution compared to current options.

What evidence suggests that allogeneic neonatal mesenchymal stromal cells (nMSCs) might be an effective treatment for Dilated Cardiomyopathy?

Research has shown that special cells from newborns, called allogeneic neonatal mesenchymal stromal cells (nMSCs), might help treat heart conditions like Dilated Cardiomyopathy. Studies have found that these cells can enhance the heart's ability to pump blood. In animal studies, heart function improved noticeably just one month after using these cells. This trial will test nMSCs in both pediatric and adult participants, exploring different dose levels to determine the most effective and safe dosage. Although more research is needed in humans, early findings are encouraging for those considering this treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

William Mahle, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06464588?cond=DCM%20-%20Dilated%20Cardiomyopathy&term=emory&rank=1

A Phase 1 Open-Label Study of the Safety of Intravenous ... This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of Dilated ...

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

Efficacy and Mode of Action of Mesenchymal Stem Cells in ... In five of these studies, MSC treatment resulted in significantly increased dP/dt, indicating increased cardiac contractility. This finding is consistent with ...

3. synapse.patsnap.com synapse.patsnap.com/drug/a7a71aa052dc4b508bec467027441125

Allogeneic Neonatal Mesenchymal Cells (Emory University) We found that cardiac parameters in the rodent ischemia model improved 1 month after nMSCs infusion, and the result is comparable with the intramyocardial ...

4. gmr.scholasticahq.com gmr.scholasticahq.com/article/123163-stem-cell-treatment-for-dilated-cardiomyopathy-a-review-of-recent-scientific-advances

Stem Cell Treatment for Dilated Cardiomyopathy: A Review of ... In sum, allogeneic MSCs have been shown as the more effective therapy for ischemic and nonischemic cardiomyopathies when contrasted with ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.117.008460

Comparison of Mesenchymal Stem Cell Efficacy in ... Mesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac ...

6. trialx.com trialx.com/clinical-trials/listings/319228/a-phase-1-open-label-study-of-the-safety-of-intravenous-allogeneic-neonatal-mesenchymal-cells-nmscs-in-young-adult-1a-and-pediatric-1b-patients-with-dilated-cardiomyopathy-dcm/

A Phase 1 Open-Label Study of the Safety of Intravenous ... This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06464588?cond=Dilated%20cardiomyopathy%201A%20OR%20%22cardiomyopathy%20dilated%20with%20conduction%20defect%20type%201%22%20OR%20%22%20cardiomyopathy,%20dilated,%20type%201A%22%20OR%20%22%20CDCD1%22%20OR%20%22%20dilated%20cardiomyopathy%20type%201A%22%20OR%20%22%20dilated%20cardiomyopathy%20with%20conduction%20defect%201%22%20OR%20%22%20familial%20dilated%20cardiomyopathy%20with%20conduction%20defect%20due%20to%20LMNA%20mutation%22%20OR%20%22%20familial%20isolated%20dilated%20cardiomyopathy%20caused%20by%20mutation%20in%20LMNA%22%20OR%20%22%20LMNA%20familial%20isolated%20dilated%20cardiomyopathy%22&aggFilters=status:not%20rec&viewType=Table&rank=2

A Phase 1 Open-Label Study of the Safety of Intravenous ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11487037/

Efficacy and safety of stem cell therapy in patients with dilated ... Stem cell therapy (SCT) for dilated cardiomyopathy shows significant improvement in left ventricular ejection fraction. Evidence on the impact of SCT on heart ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2666084921002242

Allogeneic Mesenchymal Stromal Cell Injection to Alleviate ... We report the first case of intramyocardial injection of allogeneic mesenchymal stromal cells as rescue therapy in a neonate with ischemic heart failure ...

10. stemcellsjournals.onlinelibrary.wiley.com stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.21-0094

Cell therapy for nonischemic dilated cardiomyopathy: A ... The results of this meta-analysis suggest that cell therapy is safe with no increased risk for major adverse cardiac events and may improve left ...