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Active, not recruitingNCT05774509SECRET-HFUpdated Jul 8, 2026

Treatment of Non-ischemic Cardiomyopathies by Intravenous Extracellular Vesicles of Cardiovascular Progenitor Cells

A Phase 1 interventional study of Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells in Heart Failure With Reduced Ejection Fraction, sponsored by Assistance Publique - Hôpitaux de Paris. Active, not recruiting at 1 site in France. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-08.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
All
01

Study summary

The goal of this clinical trial is to assess the safety and efficacy of three intravenous injections of the extracellulat vesicle-enriched secretome of cardiovascular progenitor cells in severely symptomatic patients with drug-refractory left ventricular (LV) dysfunction secondary to non-ischemic dilated cardiomyopathy. The main questions it aims to answer are:

  • Are these repeated injections safe and well tolerated?
  • Do they improve cardiac function and, if yes, to what extent?
Read the detailed description

The overall objective of this study is to assess the safety and efficacy of repeated intravenous injections of the secretome of cardiovascular progenitor cells in severely symptomatic patients with drug-refractory left ventricular (LV) dysfunction secondary to non-ischemic dilated cardiomyopathy.

The rationale and design of this trial are based on three main assumptions:

  1. The tissue-repair capacity of transplanted cells can be duplicated by the delivery of the extracellular vesicles (EV) that they secrete.
  2. The greatest therapeutic efficacy seems to be achieved by using secreting cells that are committed to the same lineage as those of the tissue to be repaired, hence, the use of cardiovascular progenitor cells as the source of the EV-enriched secretome.
  3. Leveraging the benefits of cells, or their secreted products, by repeated administrations requires a non-invasive approach, which highlights the potential interest of the intravenous approach.
02

Conditions studied

  • Heart Failure With Reduced Ejection Fraction
03

In context

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    Treated group

    A maximum of 12 patients will be included in the study following a dose-escalating design: * Cohort 1 (4 patients) will receive 20x10E9 particles/kg for each infusion, with a total of 3 infusions, for a cumulative dose of 60x10E9 particles/kg; * Cohort 2: in the absence of safety issues in Cohort 1, 8 patients will receive 40x10E9 particles/kg for each infusion, with a total of 3 infusions, for a cumulative dose of 120x10E9 particles/kg.

    Biological: Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells

Interventions

  • BiologicalExtracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells

    Repeated (X3) intravenous infusions of the extracellular vesicle-enriched secretome of cardiovascular progenitor cells (differentiated from human induced pluripotent stem cells)

06

What researchers measure

Primary outcomes

  1. Serious Adverse Events

    Number of any potentially Serious Adverse Events (SAEs)/Reactions attributed to the experimental treatment: death (cardiovascular or of any cause), hospitalization for worsening heart failure, acute coronary syndrome (including myocardial infarction), sustained atrial and ventricular arrhythmias, ischemic stroke, immune-allergic or infectious reactions to the intravenous infusions of the IMP, and any other potential adverse effects detected and corroborated by clinical presentation, laboratory investigations and image analysis.

    Time frame: 10 weeks after the onset of treatment: 6 weeks of treatment and 4 weeks of follow-up after the last IMP infusion.

Secondary outcomes

  1. Validation of the bioactivity of the EV-enriched secretome by proliferation of human vascular endothelial cells.

    Bioactivity of the IMP (potency tests) assessed by proliferation of human vascular endothelial cells assessed by BrdU (\>20% relative to the control).

    Time frame: 12 months

  2. Validation of the bioactivity of the EV-enriched secretome by activation of allogeneic peripheral blood mononuclear cells.

    Bioactivity of the IMP (potency tests) assessed by activation of allogeneic peripheral blood mononuclear cells assessed by the secretion of IL-2 and IFNγ (lack of increased secretion compared with the control).

    Time frame: 12 months

  3. Validation of the bioactivity of the EV-enriched secretome

    Bioactivity of the IMP (potency tests) assessed by degranulation of Natural Killer cells assessed by the expression of CD107 (compared with a negative control).

    Time frame: 12 months

  4. Assessment of the effects of the IMP on immune and inflammatory responses at 3 weeks after the onset of the treatment.

    Detection of donor-specific antibodies before the second secretome infusion.

    Time frame: 3 weeks after the onset of the treatment.

  5. Assessment of the effects of the IMP on immune and inflammatory responses at 6 weeks after the onset of the treatment.

    Detection of donor-specific antibodies before the third secretome infusion.

    Time frame: 6 weeks after the onset of the treatment.

  6. Assessment of the effects of the IMP on immune and inflammatory responses at 10 weeks after the onset of the treatment.

    Detection of donor-specific antibodies at 28 days following the last secretome infusion.

    Time frame: 10 weeks after the onset of the treatment.

  7. Assessment of the effects of the IMP on immune and inflammatory responses at 6 months after the last secretome infusion.

    Detection of donor-specific antibodies at 6 months following the last secretome infusion if DSA are detected at the 28 days post-treatment study point at MFI ≥ 5000.

    Time frame: 6 months after the last secretome infusion.

  8. Inflammatory response to IMP infusions

    Assessment of blood levels of interleukins, C- Reactive Protein and immune cells.

    Time frame: 28 days, 6 and 12 months following the third infusion

  9. Monitoring for Major Cardiovascular Adverse Events (MACE)

    MACE including cardiac death, rehospitalization for heart failure, acute coronary syndromes, ischemic stroke and ventricular arrhythmias during the 1-year follow-up.

    Time frame: 28 days following the last IMP infusion and subsequently until 1 year after the end of treatment

  10. Changes in LV function assessed by NYHA at 28 days after the end of the treatment.

    New York Heart Association (NYHA) functional class.

    Time frame: 28 days after the end of the treatment.

  11. Changes in LV function assessed by NYHA at 6 months after the end of the treatment.

    New York Heart Association (NYHA) functional class.

    Time frame: 6 months after the end of the treatment.

  12. Changes in LV function assessed by NYHA at 12 months after the end of the treatment.

    New York Heart Association (NYHA) functional class.

    Time frame: 12 months after the end of the treatment.

  13. Changes in LV function assessed by Minnesota Living With Heart Failure questionnaire at 6 months after the end of the treatment.

    Quality of life assessed by Minnesota Living With Heart Failure questionnaire.

    Time frame: 6 months after the end of the treatment.

  14. Changes in LV function assessed by Minnesota Living With Heart Failure questionnaire at 12 months after the end of the treatment.

    Quality of life assessed by Minnesota Living With Heart Failure questionnaire.

    Time frame: 12 months after the end of the treatment.

  15. Changes in LV function assessed by LV ejection fraction at 28 days after the end of the treatment.

    Measurements of LV ejection fraction (EF%) by Doppler-echocardiography.

    Time frame: 28 days after the end of the treatment.

  16. Changes in LV function assessed by LV ejection fraction at 6 months after the end of the treatment.

    Measurements of LV ejection fraction (EF%) by Doppler-echocardiography.

    Time frame: 6 months after the end of the treatment.

  17. Changes in LV function assessed by LV ejection fraction at 12 months after the end of the treatment.

    Measurements of LV ejection fraction (EF%) by Doppler-echocardiography.

    Time frame: 12 months after the end of the treatment.

  18. Changes in LV function assessed by LV Volumes at 28 days after the end of the treatment.

    LV Volumes ml/m2 by Doppler-echocardiography.

    Time frame: 28 days after the end of the treatment.

  19. Changes in LV function assessed by LV Volumes at 6 months after the end of the treatment.

    LV Volumes ml/m2 by Doppler-echocardiography.

    Time frame: 6 months after the end of the treatment.

  20. Changes in LV function assessed by LV Volumes at 12 months after the end of the treatment.

    LV Volumes ml/m2 by Doppler-echocardiography.

    Time frame: 12 months after the end of the treatment.

  21. Changes in LV function assessed by LV global longitudinal strain at 28 days after the end of the treatment.

    LV global longitudinal strain (%) by Doppler-echocardiography.

    Time frame: 28 days after the end of the treatment.

  22. Changes in LV function assessed by LV global longitudinal strain at 6 months after the end of the treatment.

    LV global longitudinal strain (%) by Doppler-echocardiography.

    Time frame: 6 months after the end of the treatment.

  23. Changes in LV function assessed by LV global longitudinal strain at 12 months after the end of the treatment.

    LV global longitudinal strain (%) by Doppler-echocardiography.

    Time frame: 12 months after the end of the treatment.

  24. Changes in LV function assessed by LV ejection fraction (%) by Cardiac Magnetic Resonance at 6 months after the end of the treatment.

    Measurements of LV ejection fraction (%) by Cardiac Magnetic Resonance.

    Time frame: 6 months after the end of the treatment.

  25. Changes in LV function assessed by LV ejection fraction (%) by Cardiac Magnetic Resonance at 12 months after the end of the treatment.

    Measurements of LV ejection fraction (%) by Cardiac Magnetic Resonance.

    Time frame: 12 months after the end of the treatment.

  26. Changes in LV function assessed by LV volumes (ml/m2) by Cardiac Magnetic Resonance at 6 months after the end of the treatment.

    LV volumes (ml/m2) by Cardiac Magnetic Resonance (CMR).

    Time frame: 6 months after the end of the treatment.

  27. Changes in LV function Changes in LV function assessed by LV volumes (ml/m2) by Cardiac Magnetic Resonance at 12 months after the end of the treatment.

    LV volumes (ml/m2) by Cardiac Magnetic Resonance (CMR).

    Time frame: 12 months after the end of the treatment.

  28. Changes in LV function assessed by the presence/extent of myocardial late-enhancement at 6 months after the end of the treatment.

    Presence/extent of myocardial late-enhancement after gadolinium administration, in the absence of contra-indication, by Cardiac Magnetic Resonance.

    Time frame: 6 months after the end of the treatment.

  29. Changes in LV function assessed by the presence/extent of myocardial late-enhancement at 12 months after the end of the treatment.

    Presence/extent of myocardial late-enhancement after gadolinium administration, in the absence of contra-indication, by Cardiac Magnetic Resonance.

    Time frame: 12 months after the end of the treatment.

  30. Changes in LV function assessed by maximum oxygen consumption at 6 months after the end of the treatment.

    Maximum oxygen consumption at exercise (mL/min/kg).

    Time frame: 6 months after the end of the treatment.

  31. Changes in LV function assessed by maximum oxygen consumption at 12 months after the end of the treatment.

    Maximum oxygen consumption at exercise (mL/min/kg).

    Time frame: 12 months after the end of the treatment.

  32. Changes in LV function assessed by Natriuretic peptide plasma levels at 28 days after the end of the treatment.

    Natriuretic peptide plasma levels (BNP or NT-ProBNP in pg/mL).

    Time frame: 28 days after the end of the treatment.

  33. Changes in LV function assessed by Natriuretic peptide plasma levels at 6 months after the end of the treatment.

    Natriuretic peptide plasma levels (BNP or NT-ProBNP in pg/mL).

    Time frame: 6 months after the end of the treatment.

  34. Changes in LV function assessed by Natriuretic peptide plasma levels at 12 months after the end of the treatment.

    Natriuretic peptide plasma levels (BNP or NT-ProBNP in pg/mL).

    Time frame: 12 months after the end of the treatment.

  35. Serious Adverse Events

    Number of any potentially Serious Adverse Events (T-SAEs)/Reactions attributed to the experimental treatment (primary endpoint) up to 12 months.

    Time frame: 12 months

07

Study locations

1 site
  • Hôpital européen Georges Pompidou
    Paris, 75015, France
08

References and documents

Publications

  • Kervadec A, Bellamy V, El Harane N, Arakelian L, Vanneaux V, Cacciapuoti I, Nemetalla H, Perier MC, Toeg HD, Richart A, Lemitre M, Yin M, Loyer X, Larghero J, Hagege A, Ruel M, Boulanger CM, Silvestre JS, Menasche P, Renault NK. Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure. J Heart Lung Transplant. 2016 Jun;35(6):795-807. doi: 10.1016/j.healun.2016.01.013. Epub 2016 Jan 19. PubMed 27041495 ↗
  • El Harane N, Kervadec A, Bellamy V, Pidial L, Neametalla HJ, Perier MC, Lima Correa B, Thiebault L, Cagnard N, Duche A, Brunaud C, Lemitre M, Gauthier J, Bourdillon AT, Renault MP, Hovhannisyan Y, Paiva S, Colas AR, Agbulut O, Hagege A, Silvestre JS, Menasche P, Renault NKE. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors. Eur Heart J. 2018 May 21;39(20):1835-1847. doi: 10.1093/eurheartj/ehy012. PubMed 29420830 ↗
  • Lima Correa B, El Harane N, Gomez I, Rachid Hocine H, Vilar J, Desgres M, Bellamy V, Keirththana K, Guillas C, Perotto M, Pidial L, Alayrac P, Tran T, Tan S, Hamada T, Charron D, Brisson A, Renault NK, Al-Daccak R, Menasche P, Silvestre JS. Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts. Cardiovasc Res. 2021 Jan 1;117(1):292-307. doi: 10.1093/cvr/cvaa028. PubMed 32049348 ↗
  • Lima Correa B, El Harane N, Desgres M, Perotto M, Alayrac P, Guillas C, Pidial L, Bellamy V, Baron E, Autret G, Kamaleswaran K, Pezzana C, Perier MC, Vilar J, Alberdi A, Brisson A, Renault N, Gnecchi M, Silvestre JS, Menasche P. Extracellular vesicles fail to trigger the generation of new cardiomyocytes in chronically infarcted hearts. Theranostics. 2021 Nov 2;11(20):10114-10124. doi: 10.7150/thno.62304. eCollection 2021. PubMed 34815807 ↗
  • Humbert C, Cordier C, Drut I, Hamrick M, Wong J, Bellamy V, Flaire J, Bakshy K, Dingli F, Loew D, Larghero J, Fabreguettes JR, Menasche P, Renault NK, Churlaud G. GMP-Compliant Process for the Manufacturing of an Extracellular Vesicles-Enriched Secretome Product Derived From Cardiovascular Progenitor Cells Suitable for a Phase I Clinical Trial. J Extracell Vesicles. 2025 Aug;14(8):e70145. doi: 10.1002/jev2.70145. PubMed 40831309 ↗

Individual participant data

Plan to share: Yes — Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Supporting information: Study protocol, Icf

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05774509
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France
Responsible party
Sponsor
First posted
Mar 17, 2023
Start date
May 31, 2023
Primary completion
Jul 10, 2026 (estimated)
Completion
Jun 15, 2027 (estimated)
Last update
Jul 8, 2026

Study contacts

Philippe Menasché, MD, PhD
principal investigator · Assistance Publique - Hôpitaux de Paris

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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