Dilated Cardiomyopathy, Heart Failure
Conditions
Brief summary
The goal of REMEDIUM project is to develop personalized stem cell therapy for patients with chronic heart failure due to dilated cardiomyopathy (DCM). The main focus of the project is (1) on repetitive administration of cell therapy that would allow for long-lasting improvements in heart function and outcome in this patient population. In parallel, the investigators aim to (2) develop a standardized patient-specific stem cell product that could be cryopreserved and stored in a stem cell bank for prolonged time periods, and used for therapeutic application when clinically indicated. By using a unique multimodality imaging platform, the goal of this project is also to (3) define standardized clinical criteria that would serve as a guideline for evaluation of the effects of stem cell therapy in future clinical trials and everyday clinical settings. Finally, to improve the clinical implementation of cell therapy,the investigators aim to (4) develop a stem cell delivery technique that could be used to treat both left and right and ventricular failure and could be implemented in a standardized fashion designed for a widespread clinical use.
Interventions
BIOLOGICALStem cell therapy
Bone marrow cells will be mobilized into peripheral blood by daily subcutaneous injections of G-CSF (10 µg/kg daily) and collected by leukapheresis. Positive immunomagnetic selection of CD34+ cells will be performed. Electroanatomic mapping of the left ventricle will be performed using the Biosense NOGA system (Biosense-Webster®, Diamond Bar, CA). The target area for cell delivery will be defined as the myocardial segments with unipolar voltage potentials ≥8.3 mV, bipolar amplitudes \>1.9 mV, and linear shortening \<6%. Intramyocardial delivery of cell suspension will be performed with the MyoStar (BiosenseWebster®, Diamond Bar, CA) injection catheter. Each patient will receive 20 injections (0.3 mL each; total volume of 6 mL). All the procedures will be repeated 6 months after baseline.
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-70 years old * Diagnosis of DCM according to European Society of Cardiology position statement * Left ventricular ejection fraction (LVEF) by echocardiography 20-40%, * New York Heart Association (NYHA) functional class heart failure II or III for at least 3 months before referral.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in left ventricular ejection fraction | baseline and 1 year | The echocardiography data will be recorded and analyzed at the end of the study by an independent echocardiographer who will be blinded to the patient's treatment status and the timing of the recordings. Left ventricular end-systolic volume and end-diastolic volume and LVEF will be estimated using the Simpson's biplane method and left ventricular end-systolic dimension and end-diastolic dimension will be measured in the parasternal long axis view. All echocardiographic measurements will be averaged for 5 cycles.. The change in left ventricular ejection fraction (LVEF) between randomization and 1 year thereafter will be assessed by 2D echocardiography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in regional wall motion | baseline and 1 year | Left ventricular segmental wall motion analysis (strain) will be evaluated with TomTec software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany), using a 17-segment model of the left ventricle. |
| Change in left ventricular dimension | 1 year | The change in left ventricular dimensions between randomization and 1 year thereafter will be assessed by 2D echocardiography. |
| Change in exercise capacity | baseline and 1 year | Change in exercise capacity will be evaluated by 6-minute walk test was performed by a blinded observer according to the standard protocol. |
| Change in NT-proBNP | baseline and 1 year | — |
Other
| Measure | Time frame |
|---|---|
| Cardiac mortality | 1 year |
| Hospitalization for heart failure | 1 year |
| Pump failure mortality | 1 year |
| Incidence of ventricular arrhythmias | 1 year |
Countries
Slovenia
Outcome results
None listed