Heart Failure With Reduced Ejection FractionPhase 1SECRET-HFNCT05774509
Treatment of Non-ischemic Cardiomyopathies by Intravenous Extracellular Vesicles of Cardiovascular Progenitor Cells
A Phase 1 study testing Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells in people with Heart Failure With Reduced Ejection Fraction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- 31 May 2023to 15 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged between 18 to 80 years
- Signed written informed consent
- French Social Security affiliation;
- 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);
- NYHA Class III in spite of optimal heart failure maximally tolerated guideline-directed medical therapy, including cardiac resynchronization if needed, without other treatment options;
- Plasma level of B-type natriuretic peptide (BNP) > 150 pg/mL or, N-terminal pro-BNP (NT-proBNP) ≥ 400 pg/mL;
- 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.
Who cannot join
- Implantation of a cardiac resynchronisation therapy device or an ICD unit during the preceding 3 months;
- 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)
- Patients treated with inotropic agents during the 1 month period prior to inclusion;
- Acute heart failure (regardless of the cause);
- Heart failure caused by cardiac valve disease, untreated hypertension or documented coronary artery disease with lesions which could explain the cardiomyopathy;
- Cardiomyopathy due to a reversible cause e.g. endocrine disease, alcohol or drug abuse, myocarditis, Tako-Tsubo, or arrhythmias;
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- Cardiomyopathy due a syndromic/systemic disease (e.g. Duchenne's muscular dystrophy, immune/inflammatory/infiltrative disorders [amyloidosis, hemochromatosis]);
- 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;
- Previous cardiac surgery;
- Recent stroke (within the last 3 months);
- Documented presence of a known LV thrombus, aortic dissection, or aortic aneurysm;
- 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;
- History of drug-induced allergic reactions or allergy of any type having required treatment;
- Contraindication to corticosteroids or anti-histaminic agents;
- Contraindication to gadoterate meglumine if it will be used with CMR;
- 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);
- Coagulopathy not due to a reversible cause;
- 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;
- Diabetes with poorly controlled blood glucose levels and/or evidence of proliferative retinopathy;
- Dialysis-dependent renal insufficiency;
- Autoimmune disorders or current immunosuppressive therapy;
- History of organ transplant or cell-based treatment;
- Serum positivity for HIV, hepatitis BsAg, or viremic hepatitis C;
- Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control;
- Active infection;
- Known allergy to aminoglycosides;
- Patient under legal protection (guardianship);
- Participation in another interventional trial;
- Life expectancy less than one year.
- Contraindication to 18FDG-PETscan
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Non-ischemic Dilated Cardiomyopathies by Intravenous Infusions of the Extracellular Vesicle-Enriched Secretome of Cardiovascular Progenitor Cells
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:
- The tissue-repair capacity of transplanted cells can be duplicated by the delivery of the extracellular vesicles (EV) that they secrete.
- 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.
- 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.
- Being tested
- Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cellsBiological
Repeated (X3) intravenous infusions of the extracellular vesicle-enriched secretome of cardiovascular progenitor cells (differentiated from human induced pluripotent stem cells)
| Study group | Role | What they receive |
|---|---|---|
| Treated group | Experimental | 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. Receives: Biological: Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 weeks after the onset of treatment: 6 weeks of treatment and 4 weeks of follow-up after the last IMP infusion.
Secondary outcomes (35)
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).
Measured: 12 months
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).
Measured: 12 months
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).
Measured: 12 months
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.
Measured: 3 weeks after the onset of the treatment.
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.
Measured: 6 weeks after the onset of the treatment.
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.
Measured: 10 weeks after the onset of the treatment.
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.
Measured: 6 months after the last secretome infusion.
Inflammatory response to IMP infusions
Assessment of blood levels of interleukins, C- Reactive Protein and immune cells.
Measured: 28 days, 6 and 12 months following the third infusion
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.
Measured: 28 days following the last IMP infusion and subsequently until 1 year after the end of treatment
Changes in LV function assessed by NYHA at 28 days after the end of the treatment.
New York Heart Association (NYHA) functional class.
Measured: 28 days after the end of the treatment.
Changes in LV function assessed by NYHA at 6 months after the end of the treatment.
New York Heart Association (NYHA) functional class.
Measured: 6 months after the end of the treatment.
Changes in LV function assessed by NYHA at 12 months after the end of the treatment.
New York Heart Association (NYHA) functional class.
Measured: 12 months after the end of the treatment.
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.
Measured: 6 months after the end of the treatment.
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.
Measured: 12 months after the end of the treatment.
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.
Measured: 28 days after the end of the treatment.
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.
Measured: 6 months after the end of the treatment.
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.
Measured: 12 months after the end of the treatment.
Changes in LV function assessed by LV Volumes at 28 days after the end of the treatment.
LV Volumes ml/m2 by Doppler-echocardiography.
Measured: 28 days after the end of the treatment.
Changes in LV function assessed by LV Volumes at 6 months after the end of the treatment.
LV Volumes ml/m2 by Doppler-echocardiography.
Measured: 6 months after the end of the treatment.
Changes in LV function assessed by LV Volumes at 12 months after the end of the treatment.
LV Volumes ml/m2 by Doppler-echocardiography.
Measured: 12 months after the end of the treatment.
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.
Measured: 28 days after the end of the treatment.
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.
Measured: 6 months after the end of the treatment.
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.
Measured: 12 months after the end of the treatment.
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.
Measured: 6 months after the end of the treatment.
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.
Measured: 12 months after the end of the treatment.
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).
Measured: 6 months after the end of the treatment.
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).
Measured: 12 months after the end of the treatment.
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.
Measured: 6 months after the end of the treatment.
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.
Measured: 12 months after the end of the treatment.
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).
Measured: 6 months after the end of the treatment.
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).
Measured: 12 months after the end of the treatment.
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).
Measured: 28 days after the end of the treatment.
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).
Measured: 6 months after the end of the treatment.
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).
Measured: 12 months after the end of the treatment.
Serious Adverse Events
Number of any potentially Serious Adverse Events (T-SAEs)/Reactions attributed to the experimental treatment (primary endpoint) up to 12 months.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2023
- Study start31 May 2023
- Primary completion10 Jul 2026 (estimated)
- Study completion15 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Philippe Menasché, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05774509
- Sponsor's protocol ID
- APHP200034
- Other IDs
- 2022-001844-75, PHRC-19-0330
- Acronym
- SECRET-HF
- Status last verified
- Jul 2026
- First submitted
- 20 Feb 2023
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
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 27041495El 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 29420830Lima 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 32049348Lima 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 34815807Humbert 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Non-ischemic Dilated Cardiomyopathies by Intravenous Infusions of the Extracellular Vesicle-Enriched Secretome of Cardiovascular Progenitor Cells
- ClinicalTrials.gov ID
- NCT05774509
- Acronym / sponsor ID
- SECRET-HF / APHP200034
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- 31 May 2023 (actual)
- Primary completion
- 10 Jul 2026 (estimated)
- Study completion
- 15 Jun 2027 (estimated)
- First posted
- 17 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?
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:
- The tissue-repair capacity of transplanted cells can be duplicated by the delivery of the extracellular vesicles (EV) that they secrete.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treated group | Experimental | Biological: Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cellsA 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged between 18 to 80 years
- Signed written informed consent
- French Social Security affiliation;
- 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);
- NYHA Class III in spite of optimal heart failure maximally tolerated guideline-directed medical therapy, including cardiac resynchronization if needed, without other treatment options;
Key exclusion criteria (30 listed)
- Implantation of a cardiac resynchronisation therapy device or an ICD unit during the preceding 3 months;
- 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)
- Patients treated with inotropic agents during the 1 month period prior to inclusion;
- Acute heart failure (regardless of the cause);
- Heart failure caused by cardiac valve disease, untreated hypertension or documented coronary artery disease with lesions which could explain the cardiomyopathy;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cellsRepeated (X3) intravenous infusions of the extracellular vesicle-enriched secretome of cardiovascular progenitor cells (differentiated from human induced pluripotent stem cells) | Biological | Treated group |
Primary outcome
Serious Adverse Events
Time frame: 10 weeks after the onset of treatment: 6 weeks of treatment and 4 weeks of follow-up after the last IMP infusion.
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.
35 secondary outcomes
Validation of the bioactivity of the EV-enriched secretome by proliferation of human vascular endothelial cells.
Time frame: 12 months
Validation of the bioactivity of the EV-enriched secretome by activation of allogeneic peripheral blood mononuclear cells.
Time frame: 12 months
Validation of the bioactivity of the EV-enriched secretome
Time frame: 12 months
Assessment of the effects of the IMP on immune and inflammatory responses at 3 weeks after the onset of the treatment.
Time frame: 3 weeks after the onset of the treatment.
Assessment of the effects of the IMP on immune and inflammatory responses at 6 weeks after the onset of the treatment.
Time frame: 6 weeks after the onset of the treatment.
Assessment of the effects of the IMP on immune and inflammatory responses at 10 weeks after the onset of the treatment.
Time frame: 10 weeks after the onset of the treatment.
Assessment of the effects of the IMP on immune and inflammatory responses at 6 months after the last secretome infusion.
Time frame: 6 months after the last secretome infusion.
Inflammatory response to IMP infusions
Time frame: 28 days, 6 and 12 months following the third infusion
Monitoring for Major Cardiovascular Adverse Events (MACE)
Time frame: 28 days following the last IMP infusion and subsequently until 1 year after the end of treatment
Changes in LV function assessed by NYHA at 28 days after the end of the treatment.
Time frame: 28 days after the end of the treatment.
Changes in LV function assessed by NYHA at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by NYHA at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by Minnesota Living With Heart Failure questionnaire at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by Minnesota Living With Heart Failure questionnaire at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by LV ejection fraction at 28 days after the end of the treatment.
Time frame: 28 days after the end of the treatment.
Changes in LV function assessed by LV ejection fraction at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by LV ejection fraction at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by LV Volumes at 28 days after the end of the treatment.
Time frame: 28 days after the end of the treatment.
Changes in LV function assessed by LV Volumes at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by LV Volumes at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by LV global longitudinal strain at 28 days after the end of the treatment.
Time frame: 28 days after the end of the treatment.
Changes in LV function assessed by LV global longitudinal strain at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by LV global longitudinal strain at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by LV ejection fraction (%) by Cardiac Magnetic Resonance at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by LV ejection fraction (%) by Cardiac Magnetic Resonance at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by LV volumes (ml/m2) by Cardiac Magnetic Resonance at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
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.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by the presence/extent of myocardial late-enhancement at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by the presence/extent of myocardial late-enhancement at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by maximum oxygen consumption at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by maximum oxygen consumption at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Changes in LV function assessed by Natriuretic peptide plasma levels at 28 days after the end of the treatment.
Time frame: 28 days after the end of the treatment.
Changes in LV function assessed by Natriuretic peptide plasma levels at 6 months after the end of the treatment.
Time frame: 6 months after the end of the treatment.
Changes in LV function assessed by Natriuretic peptide plasma levels at 12 months after the end of the treatment.
Time frame: 12 months after the end of the treatment.
Serious Adverse Events
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Background: PubMed 27041495Kervadec 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.
- Background: PubMed 29420830El 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.
- Background: PubMed 32049348Lima 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.
- Background: PubMed 34815807Lima 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.
- Derived from this study: PubMed 40831309Humbert 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.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Menasché, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Extracellular vesicle-enriched secretome of cardiovascular progenitor cells differentiated from induced pluripotent stem cells in people with Heart Failure With Reduced Ejection Fraction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious Adverse Events (time frame: 10 weeks after the onset of treatment: 6 weeks of treatment and 4 weeks of follow-up after the last IMP infusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05774509, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.