Heart Failure With Normal Ejection FractionPhase 2CELLpEFNCT02923609
Cell Therapy in HFpEF
A Phase 2 study testing Cell Therapy in people with Heart Failure With Normal Ejection Fraction, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The primary objective of the study is to investigate safety and efficacy of transendocardial CD34+ cell therapy in patients with HFpEF by evaluating changes in myocardial structure and function, patient exercise capacity and clinical outcome. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Heart Failure With Normal Ejection Fraction
- What is being tested?
- Cell Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSlovenia
- Study dates
- Jan 2016to Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Preserved left ventricular systolic function on echocardiography (LVEF>50%)
- Evidence of diastolic dysfunction by echocardiography (E/e'>15)
- Symptoms of heart failure
- NT-proBNP levels >300 pg/ml
- absence of permanent atrial fibrillation
Who cannot join
- acute multi-organ failure
- history of any malignant disease within 5 years
- diminished functional capacity due to non-cardiac co-morbidities (COPD, PAOD, morbid obesity)
- pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A PILOT TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
The primary objective of the study is to investigate safety and efficacy of transendocardial CD34+ cell therapy in patients with HFpEF by evaluating changes in myocardial structure and function, patient exercise capacity and clinical outcome.
The safety end-points include serious adverse events (SAEs), defined as any serious event that may result in persistent or significant disability or incapacity and included death, heart transplantation, sustained ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and heart failure exacerbation requiring hospitalization.
Read the detailed description
In all patients, peripheral blood stem cells will be mobilized by daily subcutaneous injections of G-CSF (10 mcg/kg, divided b.i.d) for 5 days. Peripheral blood stem cells will then be collected with Miltenyi cell separator (Miltenyi Biotech, Germany) and the magnetic cell separator Isolex 300i (Nexell Therapeutics Inc., California, USA) will be used for the immunomagnetic positive selection of the CD34+ cells.
- Being tested
- Cell Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cell TherapyBiological
Electro-anatomical mapping will be performed using the Biosense NOGA system (Biosense-Webster, Diamond Bar, California). Local diastolic function will be assessed by a novel algorhithm that allows for the measuring local ventricular relaxation times at each of the sampling points. Target areas for cell delivery will be defined as the myocardial segments with the evidence of local diastolic dysfunction and myocardial hibernation. Transendocardial delivery of cell suspension in the SC Group will be performed with MyoStar® (Biosense Webster) injection catheter. Each patient will receive 20 injections of 0.3 mL of stem cell suspension.
| Study group | Role | What they receive |
|---|---|---|
| SC Group | Experimental | In Phase 1 of the study, all patients will be treated with optimization of medical therapy for 6 months. Thereafter, all patients will cros over to Phase 2 of the study, where they will receive transendocardial CD34+ cell therapy. Follow-up of Phase 2 will last for 6 months. At the time of enrollment (6 months before cell therapy), at time of cell therapy, and 6 months thereafter we will perform detailed clinical evaluation, laboratory assays, echocardiography, 6-minute walk test, and measure plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP). Receives: Biological: Cell Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular filling pressures (E/e') assessed by echocardiography
The E/e' ratio will be calculated from early transmitral velocity divided by peak left ventricular relaxation velocity for estimation of the left ventricular filling pressure.
Measured: Baseline, 6 months and 1 year
Secondary outcomes (4)
Change in exercise capacity
6-minute walk test will be performed by a blinded observer according to the standard protocol.
Measured: Baseline, 6 months and 1 year
Change in NT-proBNP levels
NT-proBNP assays will be performed at a central independent laboratory, blinded to the patient's clinical data using a commercially available kit (Roche Diagnostics, Mannheim, Germany).
Measured: Baseline, 6 months and 1 year
Change in systolic strain
Left ventricular longitudinal strains will be analyzed by speckle tracking echocardiography from apical four-chamber, two-chamber, and long-axis views.
Measured: Baseline, 6 months and 1 year
Change in diastolic dysfunction grade
Diastolic dysfunction will be graded according based on E/A ratio and left atrial pressure estimation.
Measured: Baseline, 6 months and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study startJan 2016
- Primary completionJan 2022
- Study completionMar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Normal Ejection FractionStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The study is designed in a prospective crossover fashion. In Phase 1 of the study, all patients are treated with optimization of medical therapy for 6 months. Thereafter, all patients cross over to Phase 2 of the study, where they receive transendocardial CD34+ cell therapy. Follow-up of Phase 2 lasts for 6 months. At the time of enrollment (6 months before cell therapy), at time of cell therapy, and 6 months thereafter we will perform detailed clinical evaluation, laboratory assays, echocardiography, 6-minute walk test, and measure plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP).
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bojan Vrtovec, University Medical Centre Ljubljana
- Investigators
- Bojan Vrtovec, MD, PhD, Principal investigator, Department of Cardiology, UMC Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02923609
- Sponsor's protocol ID
- CELLpEF
- Acronym
- CELLpEF
- Status last verified
- May 2023
- First submitted
- 3 Oct 2016
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Vrtovec B, Frljak S, Poglajen G, Zemljic G, Cerar A, Sever M, Haddad F, Wu JC. A pilot clinical trial of cell therapy in heart failure with preserved ejection fraction. Eur J Heart Fail. 2022 Aug;24(8):1441-1449. doi: 10.1002/ejhf.2596. Epub 2022 Jul 20.
PubMed 35775390
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PILOT TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
- ClinicalTrials.gov ID
- NCT02923609
- Acronym / sponsor ID
- CELLpEF / CELLpEF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- Jan 2022 (actual)
- Study completion
- Mar 2022 (actual)
- First posted
- 4 Oct 2016 (estimated)
- 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 primary objective of the study is to investigate safety and efficacy of transendocardial CD34+ cell therapy in patients with HFpEF by evaluating changes in myocardial structure and function, patient exercise capacity and clinical outcome.
The safety end-points include serious adverse events (SAEs), defined as any serious event that may result in persistent or significant disability or incapacity and included death, heart transplantation, sustained ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and heart failure exacerbation requiring hospitalization.
Detailed description
In all patients, peripheral blood stem cells will be mobilized by daily subcutaneous injections of G-CSF (10 mcg/kg, divided b.i.d) for 5 days. Peripheral blood stem cells will then be collected with Miltenyi cell separator (Miltenyi Biotech, Germany) and the magnetic cell separator Isolex 300i (Nexell Therapeutics Inc., California, USA) will be used for the immunomagnetic positive selection of the CD34+ cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study is designed in a prospective crossover fashion. In Phase 1 of the study, all patients are treated with optimization of medical therapy for 6 months. Thereafter, all patients cross over to Phase 2 of the study, where they receive transendocardial CD34+ cell therapy. Follow-up of Phase 2 lasts for 6 months. At the time of enrollment (6 months before cell therapy), at time of cell therapy, and 6 months thereafter we will perform detailed clinical evaluation, laboratory assays, echocardiography, 6-minute walk test, and measure plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP).
| Arm | Type | Receives |
|---|---|---|
| SC Group | Experimental | Biological: Cell TherapyIn Phase 1 of the study, all patients will be treated with optimization of medical therapy for 6 months. Thereafter, all patients will cros over to Phase 2 of the study, where they will receive transendocardial CD34+ cell therapy. Follow-up of Phase 2 will last for 6 months. At the time of enrollment (6 months before cell therapy), at time of cell therapy, and 6 months thereafter we will perform detailed clinical evaluation, laboratory assays, echocardiography, 6-minute walk test, and measure plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Preserved left ventricular systolic function on echocardiography (LVEF>50%)
- Evidence of diastolic dysfunction by echocardiography (E/e'>15)
- Symptoms of heart failure
- NT-proBNP levels >300 pg/ml
- absence of permanent atrial fibrillation
Key exclusion criteria (4 listed)
- acute multi-organ failure
- history of any malignant disease within 5 years
- diminished functional capacity due to non-cardiac co-morbidities (COPD, PAOD, morbid obesity)
- pregnancy
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 |
|---|---|---|
| Cell TherapyElectro-anatomical mapping will be performed using the Biosense NOGA system (Biosense-Webster, Diamond Bar, California). Local diastolic function will be assessed by a novel algorhithm that allows for the measuring local ventricular relaxation times at each of the sampling points. Target areas for cell delivery will be defined as the myocardial segments with the evidence of local diastolic dysfunction and myocardial hibernation. Transendocardial delivery of cell suspension in the SC Group will be performed with MyoStar® (Biosense Webster) injection catheter. Each patient will receive 20 injections of 0.3 mL of stem cell suspension. | Biological | SC Group |
Primary outcome
Change in left ventricular filling pressures (E/e') assessed by echocardiography
Time frame: Baseline, 6 months and 1 year
The E/e' ratio will be calculated from early transmitral velocity divided by peak left ventricular relaxation velocity for estimation of the left ventricular filling pressure.
4 secondary outcomes
Change in exercise capacity
Time frame: Baseline, 6 months and 1 year
Change in NT-proBNP levels
Time frame: Baseline, 6 months and 1 year
Change in systolic strain
Time frame: Baseline, 6 months and 1 year
Change in diastolic dysfunction grade
Time frame: Baseline, 6 months and 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Derived from this study: PubMed 35775390Vrtovec B, Frljak S, Poglajen G, Zemljic G, Cerar A, Sever M, Haddad F, Wu JC. A pilot clinical trial of cell therapy in heart failure with preserved ejection fraction. Eur J Heart Fail. 2022 Aug;24(8):1441-1449. doi: 10.1002/ejhf.2596. Epub 2022 Jul 20.
- Individual participant dataSharing planned: No
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HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
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Recruiting
PrEcision Pacing in HFpEF: the PEP-HFpEF Trial
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Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity
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Active, not recruiting
Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction
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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.
Bojan Vrtovec, MD, PhD principal investigator
Department of Cardiology, UMC Ljubljana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cell Therapy in people with Heart Failure With Normal Ejection Fraction, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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 5 inclusion and 4 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: finished, as of the sponsor's last update on 10 May 2023. 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 Slovenia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in left ventricular filling pressures (E/e') assessed by echocardiography (time frame: Baseline, 6 months and 1 year). 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 NCT02923609, which also lists 1 linked publication.
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 10 May 2023.