Treatment for heart failure using cell-derived vesicles

Treatment of Non-ischemic Dilated Cardiomyopathies by Intravenous Infusions of the Extracellular Vesicle-Enriched Secretome of Cardiovascular Progenitor Cells

This study is testing if special cell-derived injections can help improve heart function in people with severe heart failure who haven't found relief from regular medications.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, radiation
• Locations: 1 site (Paris)
• Trial ID: NCT05774509 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of three intravenous injections of extracellular vesicle-enriched secretome derived from cardiovascular progenitor cells in patients suffering from severe heart failure due to non-ischemic dilated cardiomyopathy. The study will assess whether these injections are well tolerated and if they can improve cardiac function in patients who have not responded to standard drug therapies. The approach is based on the premise that the therapeutic effects of transplanted cells can be mimicked by their secreted vesicles, providing a non-invasive treatment option for heart repair.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with drug-refractory left ventricular dysfunction due to non-ischemic dilated cardiomyopathy.

Not a fit: Patients with heart failure due to ischemic causes or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve heart function and quality of life for patients with severe heart failure.

How similar studies have performed: While the use of extracellular vesicles in cardiac repair is a novel approach, similar studies have shown promise in other areas of regenerative medicine.

Eligibility criteria

Inclusion Criteria:

1. Aged between 18 to 80 years
2. Signed written informed consent
3. French Social Security affiliation;
4. Dilated cardiomyopathy defined by a dilated LV with a reduced EF ≤40% on echocardiography and/or CMR imaging, unexplained by pressure or volume overload (severe arterial hypertension or significant valve disease), coronary artery disease (as assessed by coronary angiography) or a systemic disease; in case of chemotherapy-induced cardiomyopathy, patients should have a period of at least two years of clinical cancer-free state\* and a low estimated likelihood of recurrence (≤30% at 5 years), as determined by an oncologist, based on tumor type, response to therapy, and negative metastatic work-up at the time of diagnosis (\*exceptions to this are carcinoma in situ or fully resected basal and squamous cell cancer of the skin);
5. NYHA Class III in spite of optimal heart failure maximally tolerated guideline-directed medical therapy, including cardiac resynchronization if needed, without other treatment options;
6. Plasma level of B-type natriuretic peptide (BNP) \> 150 pg/mL or, N-terminal pro-BNP (NT-proBNP) ≥ 400 pg/mL;
7. For child-bearing aged women, efficient contraception such as combined (estrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception associated with inhibition of ovulation and for men efficient contraception such as condom, during treatment and until the end of the relevant systemic exposure, i.e. until 3 months after the end of treatment.

Exclusion Criteria:

1. Implantation of a cardiac resynchronisation therapy device or an ICD unit during the preceding 3 months;
2. End-stage heart failure with reduced EF (HFrEF) defined as patients with American College of Cardiology Foundation/American Heart Association (ACCF/AHA) stage D (candidates for specialized interventions, including heart transplantation and mechanical assistance) or terminal HF (advanced HF with poor response to all forms of treatment, frequent hospitalizations and life expectancy \< 12 months)
3. Patients treated with inotropic agents during the 1 month period prior to inclusion;
4. Acute heart failure (regardless of the cause);
5. Heart failure caused by cardiac valve disease, untreated hypertension or documented coronary artery disease with lesions which could explain the cardiomyopathy;
6. Cardiomyopathy due to a reversible cause e.g. endocrine disease, alcohol or drug abuse, myocarditis, Tako-Tsubo, or arrhythmias;
7. Cardiomyopathy due a syndromic/systemic disease (e.g. Duchenne's muscular dystrophy, immune/inflammatory/infiltrative disorders \[amyloidosis, hemochromatosis\]);
8. If post-chemotherapy cardiomyopathy: a history of radiation therapy AND evidence of constrictive physiology; a baseline computerized tomography scan or CMR showing new tumor or suspicious lymphadenopathy raising concern of malignancy; a trastuzumab treatment within the last 3 months;
9. Previous cardiac surgery;
10. Recent stroke (within the last 3 months);
11. Documented presence of a known LV thrombus, aortic dissection, or aortic aneurysm;
12. Uncontrolled ventricular tachycardia defined by sustained ventricular tachycardia, including electrical storm and incessant ventricular tachycardia with no response to antiarrhythmic medication; Internal Cardioverter Defibrillator firing in the 30 days prior to the first infusion;
13. History of drug-induced allergic reactions or allergy of any type having required treatment;
14. Contraindication to corticosteroids or anti-histaminic agents;
15. Contraindication to gadoterate meglumine if it will be used with CMR;
16. Hematological disease: anaemia (haematocrit \< 25%), leukopenia (leucocytes \< 2,500/μL) or thrombocytopenia (thrombocytes \< 100,000/μL); myeloproliferative disorders, myelodysplastic syndrome, acute or chronic leukaemia, and plasma cell dyscrasias (multiple myeloma);
17. Coagulopathy not due to a reversible cause;
18. Diminished functional capacity for other reasons such as: Chronic Obstructive Pulmonary Disease (COPD) with Forced Expiratory Volume (FEV) \<1 L/min, moderate to severe claudication or morbid obesity;
19. Diabetes with poorly controlled blood glucose levels and/or evidence of proliferative retinopathy;
20. Dialysis-dependent renal insufficiency;
21. Autoimmune disorders or current immunosuppressive therapy;
22. History of organ transplant or cell-based treatment;
23. Serum positivity for HIV, hepatitis BsAg, or viremic hepatitis C;
24. Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control;
25. Active infection;
26. Known allergy to aminoglycosides;
27. Patient under legal protection (guardianship);
28. Participation in another interventional trial;
29. Life expectancy less than one year.
30. Contraindication to 18FDG-PETscan

Where this trial is running

Paris

• Hôpital européen Georges Pompidou — Paris, France (Recruiting)

Study contacts

• Principal investigator: Philippe Menasché, MD, PhD — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Touria EL AAMRI

Conditions Heart Failure With Reduced Ejection Fraction