CardiAMP Cell Therapy for Heart Failure

Overseen By Debby Holmes-Higgin, MS, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: BioCardia, Inc.

Must be taking: Heart failure medications

Disqualifiers: Non-candidate for catheterization, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

250 Participants Needed

Trial Summary

What is the purpose of this trial?

Concentrated autologous bone marrow mononuclear cells (ABM MNC) contain potentially therapeutic cell factors and past studies support therapeutic benefit to patients with cardiac diseases of acute myocardial infarction, ischemia, and heart failure when utilized as this study is designed. The purpose of the study is to determine the safety and efficacy of CardiAMP cell therapy system in patients with ischemic heart failure. It is a prospective, multi-center, randomized, controlled, patient and evaluator-blinded study comparing treatment with the CardiAMP cell therapy system to a control procedure with diagnostic catheterization.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been on stable heart failure therapy for at least three months before joining. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the CardiAMP cell therapy treatment for heart failure?

Research shows that cell therapy can improve quality of life for heart failure patients, especially those with advanced heart conditions, by reducing symptoms and hospitalizations. Although initial trials did not show significant improvements, ongoing studies suggest that optimizing cell selection and delivery methods could enhance effectiveness. ^{1 2 3 4 5}

Is CardiAMP Cell Therapy safe for humans?

Clinical trials suggest that CardiAMP Cell Therapy is generally safe, but there may be some risks like irregular heartbeats and other heart-related issues. The therapy has been tested for heart conditions, and while it shows promise, it's important to consider these potential side effects. ^{2 6 7 8 9}

How does the CardiAMP cell therapy treatment for heart failure differ from other treatments?

CardiAMP cell therapy is unique because it uses a patient's own bone marrow cells to regenerate heart muscle, aiming to restore heart function by directly injecting these cells into the heart. This approach is different from traditional treatments like medication or surgery, as it focuses on repairing the heart tissue itself rather than just managing symptoms. ^{2 4 10 11 12}

Research Team

Amish Raval, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for people with heart failure due to past heart attacks, who have a weak pumping function (ejection fraction between 20-40%), and certain blood test results. They must be on stable heart medications for at least three months. It's not open to those outside these criteria.

Inclusion Criteria

My heart's pumping ability is reduced but not severely impaired.

I have been on a stable heart failure treatment for at least 3 months.

My heart condition moderately affects my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive left ventricular catheterization with treatment consisting of autologous bone marrow mononuclear cells (ABM MNC) processed and delivered using the CardiAMP cell therapy system

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of functional capacity and quality of life

12-24 months

Extension

Participants may continue to be monitored for long-term outcomes such as all-cause death, heart failure hospitalizations, and quality of life changes

Up to 24 months

Treatment Details

Interventions

• CardiAMP cell therapy system

Trial Overview The study tests if injecting one's own processed bone marrow cells into the heart can improve its function in patients with ischemic heart failure. Participants are randomly assigned to receive either this cell therapy or just a diagnostic procedure.

Participant Groups

Group I: Study (ABM MNC) Treatment Experimental Treatment 1 Intervention

Left ventricular catheterization with treatment consisting of autologous bone marrow mononuclear cells (ABM MNC) processed and delivered using the CardiAMP cell therapy system

Group II: Control Treatment Placebo Group 1 Intervention

Left ventricular (diagnostic) catheterization but no administration of ABM MNC

CardiAMP cell therapy system is already approved in United States for the following indications:

Approved in United States as CardiAMP for:

• Ischemic heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

BioCardia, Inc.

Lead Sponsor

Trials

6

Recruited

790+

Findings from Research

Interventional heart failure therapies, including mechanical assist devices and heart transplantation, are crucial for treating end-stage refractory heart failure when drug therapies are insufficient.

Emerging treatments like cellular or stem cell therapy show promise for heart failure, alongside the importance of palliative care and self-care strategies in managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The new concept of ''interventional heart failure therapy'': part 2--inotropes, valvular disease, pumps, and transplantation. Thompson, KA., Philip, KJ., Simsir, S., et al.[2010]

Cardiac cell therapy has been shown to be safe and offers encouraging efficacy results in restoring heart function for patients with chronic heart failure and acute myocardial infarction.

To maximize the benefits of cardiac cell therapy, it is crucial to address three main challenges: preventing cell migration, increasing cell survival, and enhancing integration into the heart tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perspectives in cardiac cell therapy]. Menasché, P.[2016]

Cell therapy for heart failure has shifted from the idea of replacing dead heart cells to focusing on the beneficial factors that these cells secrete, which help the body repair itself.

Initial clinical trials using various cell sources have not shown clear improvements in heart failure outcomes, but the data collected can help refine future therapies by selecting the best cells and improving how they are delivered to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell therapy in heart failure:where do they stand? Menasché, P.[2019]

Myocardial cell therapy shows promise for regenerating heart muscle and improving heart function, especially in small animal models, but its success in human patients, particularly the elderly, has been limited.

The challenges in translating cardiac cell therapy from research to clinical practice may be due to the use of autologous cells from older patients, which are affected by aging processes, raising questions about the therapy's effectiveness for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac cell therapy: a realistic concept for elderly patients? Stamm, C., Nasseri, B., Drews, T., et al.[2021]

In the CHART-1 clinical trial involving 249 patients with ischemic heart failure, cardiopoiesis-guided cell therapy showed comparable improvements in health-related quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) when compared to a sham procedure, although the overall difference was not statistically significant (P = .107).

However, patients with advanced left ventricular enlargement experienced a significant benefit from cell therapy, with a mean treatment difference of -6.4 points on the MLHFQ (P = .009), indicating that this subgroup may particularly benefit from cell therapy in terms of both quality of life and reduced rates of death and hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell Therapy Improves Quality-of-Life in Heart Failure: Outcomes From a Phase III Clinical Trial. Yamada, S., Bartunek, J., Povsic, TJ., et al.[2023]

The CardiAMP Heart Failure trial demonstrated that personalized marrow-derived cell therapy is feasible and well tolerated in patients with chronic heart failure after a myocardial infarction, with no serious adverse events reported in the initial cohort of 10 patients.

Patients showed significant improvement in their 6-minute walk distance at 6 months (+47.8 m) and trends toward better heart function and quality of life, suggesting potential benefits of this treatment approach for heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort. Raval, AN., Johnston, PV., Duckers, HJ., et al.[2021]

Cell transplantation shows promise for treating ischemic cardiomyopathy, with clinical studies indicating benefits like improved heart function and blood flow.

While the overall safety profile of cell transplantation is high, there are potential risks such as ventricular arrhythmias and other adverse effects that can be influenced by factors like the type of cells used and the method of delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential hazards and technical considerations associated with myocardial cell transplantation protocols for ischemic myocardial syndrome. Ben-Dor, I., Fuchs, S., Kornowski, R.[2007]

The study developed a new manufacturing method for isolating bone marrow-derived mononuclear cells (BM-MNC) that significantly improved the purity of the cell product by effectively removing contaminant granulocytes and platelets.

This optimization led to a higher frequency of important cell types (CD34+ and CD133+ cells) and functional precursors, enhancing the quality of the advanced therapy medicinal product (ATMP) for use in cardiovascular cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function. Radrizzani, M., Lo Cicero, V., Soncin, S., et al.[2021]

In a review of 35 clinical trials involving 2,472 patients, the incidence of periprocedural adverse events (AEs) during intracoronary cell transplantation for myocardial infarction (MI) was found to be 7.5%, while granulocyte colony-stimulating factor (GCS-F) administration for cell mobilization had a higher incidence of 16%.

For ischemic cardiomyopathy (iCMP), periprocedural AEs were much less common at 2.6%, suggesting that the method of cell therapy administration significantly impacts safety, and that avoiding the intracoronary route may reduce the risk of AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periprocedural adverse events in cell therapy trials in myocardial infarction and cardiomyopathy: a systematic review. Alvarez, PA., Schwarz, ER., Ramineni, R., et al.[2021]

Cardiac cell therapy, which involves injecting stem cells to restore heart function, has been shown to be safe and has produced encouraging efficacy results in treating chronic heart failure and acute myocardial infarction.

Key challenges remain in optimizing this therapy, including preventing cell migration, increasing cell survival, and improving integration of the injected cells into the heart tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perspectives in cardiac cell therapy]. Menasché, P.[2016]

Cardiac transplantation is the only definitive treatment for end-stage heart failure, but due to organ shortages, patients often face long waiting periods that may require temporary circulatory support.

Emerging treatments like autologous skeletal myoblast transplantation show promise based on experimental data, but their clinical benefits need further validation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical treatment and transplantation in heart failure]. Menasché, P., Pavie, A.[2007]

Autologous bone marrow cell transplantation shows significant benefits for patients with chronic coronary artery disease, including improved heart function, reduced infarct size, and enhanced physical ability, with no observed side effects.

The therapy works through multiple mechanisms, such as direct differentiation into heart cells and stimulation of existing cardiac stem cells, making it a promising option for heart tissue regeneration after myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stem cell therapy for cardiovascular diseases. Experiences in Düsseldorf]. Schannwell, CM.[2008]

References

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

The new concept of ''interventional heart failure therapy'': part 2--inotropes, valvular disease, pumps, and transplantation. [2010]

2. France pubmed.ncbi.nlm.nih.gov

[Perspectives in cardiac cell therapy]. [2016]

3. France pubmed.ncbi.nlm.nih.gov

Cell therapy in heart failure:where do they stand? [2019]

4. England pubmed.ncbi.nlm.nih.gov

Cardiac cell therapy: a realistic concept for elderly patients? [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cell Therapy Improves Quality-of-Life in Heart Failure: Outcomes From a Phase III Clinical Trial. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort. [2021]

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

Potential hazards and technical considerations associated with myocardial cell transplantation protocols for ischemic myocardial syndrome. [2007]

8. England pubmed.ncbi.nlm.nih.gov

Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Periprocedural adverse events in cell therapy trials in myocardial infarction and cardiomyopathy: a systematic review. [2021]

10. France pubmed.ncbi.nlm.nih.gov

[Perspectives in cardiac cell therapy]. [2016]

11. France pubmed.ncbi.nlm.nih.gov

[Surgical treatment and transplantation in heart failure]. [2007]

12. Germany pubmed.ncbi.nlm.nih.gov

[Stem cell therapy for cardiovascular diseases. Experiences in Düsseldorf]. [2008]