Cell Therapy and Myocardial Recovery in Heart Failure Patients Undergoing Left Ventricular Assist Device Support
- Conditions
- Heart FailureMechanical Circulatory Support
- Interventions
- Biological: CD34+ stem cell therapy
- Registration Number
- NCT06154044
- Lead Sponsor
- University Medical Centre Ljubljana
- Brief Summary
The goal of CELL-VAD Pilot trial is to investigate a personalized stem cell therapy approach for patients with advanced non-ischemic chronic heart failure (NICM) who are supported by LVAD. In the clinical trial, the investigators aim to enroll 10 patients with NICM, scheduled for LVAD implantation. After successful LVAD implantation, patients will be enrolled and followed for 2 months to allow for postoperative rehabilitation and heart failure medical therapy and LVAD support optimization. All patients will then undergo autologous CD34+ cell therapy which will be intracoronaryly delivered to the target myocardium using NOGA electromechanical mapping system. All patients will be followed for 6 months after cell therapy. At baseline, and at 1, 3, and 6 months after cell therapy, the investigators will perform comprehensive clinical evaluation.
- Detailed Description
PROBLEM IDENTIFICATION Left ventricular assist device (LVAD) technology has evolved significantly and represents a standard of care for patients with advanced chronic heart failure. However, a significant discrepancy exists between structural and functional recovery of the failing myocardium, as only a small fraction (2%) of LVAD-supported patients demonstrate reverse structural remodeling and eventually reach clinically significant and stable functional improvement that allows for LVAD removal. Thus, there is a significant unmet need to define better the mechanisms of myocardial reverse remodeling in advanced chronic heart failure patients undergoing LVAD support.
OBJECTIVES
The goal of CELL-VAD Pilot trial is to investigate a personalized stem cell therapy approach for patients with advanced non-ischemic chronic heart failure (NICM) who are supported by LVAD. The investigators propose a Phase II non-randomized single-center clinical study focusing on (1) the administration of stem cell therapy that would allow for durable improvements in heart function and structure in NICM-LVAD patients. By using integrated analysis of multimodality imaging and biomarkers of fibrosis and angiogenesis, this project aims to (2) better define the pathophysiological mechanisms involved in myocardial recovery. Additionally, the investigators also aim to (3) define the safety parameters of stem cell therapy in NICM-LVAD patients. Based on these aims, the specific objectives of the CELL-VAD Pilot trial are:
The primary objective of this study is to investigate the safety and efficacy of stem cell therapy in NICM-LVAD patients, by evaluating changes in left ventricular structure and function, biomarkers of neurohormonal activation, patient exercise capacity, and clinical outcome.
The secondary objective of this study is to better define pathophysiological mechanisms involved in myocardial recovery in NICM-LVAD patients, by evaluating temporal changes in myocardial perfusion and in biomarkers of myocardial fibrosis in angiogenesis.
STUDY DESIGN The CELL-VAD Pilot trial consists of a clinical trial (WP1) and a multimodality imaging platform (WP2). The overall duration of the project is 3 years (36 months).
In the clinical trial, the investigators aim to enroll 10 patients with NICM, scheduled for LVAD implantation. After successful LVAD implantation, patients will be enrolled and followed for 2 months to allow for postoperative rehabilitation and heart failure medical therapy and LVAD support optimization. All patients will then undergo autologous CD34+ cell therapy which will be delivered via the intracoronary route. All patients will be followed for 6 months after cell therapy. At baseline, and at 1, 3, and 6 months after cell therapy, the investigators will perform comprehensive clinical evaluation. Clinical, biochemical, biomarker-related, imaging, and myocardial histology data will be transferred to a secured central database.
The investigators also aim to develop a personalized multimodality imaging platform by integrating the data obtained from advanced echocardiography and PET imaging.
EXPECTED OUTCOMES The investigators expect to demonstrate that in NICM-LVAD patients transendocardial autologous CD34+ cell therapy is safe and efficient, promoting the structural and functional reverse remodelling of the failing myocardium. Additionally, the results of this trial will establish a solid framework of knowledge and expertise for future clinical trials to build on.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm CD34+ stem cell therapy After successful LVAD implantation, patients will be enrolled and followed for 2 months to allow for postoperative rehabilitation and heart failure medical therapy and LVAD support optimization. All patients will then undergo autologous CD34+ cell therapy which will be delivered via intracoronary route. All patients will be followed for 6 months after cell therapy. At baseline, and at 1, 3 and 6 months after cell therapy, we will perform comprehensive clinical evaluation. Clinical, biochemical, biomarker-related, imaging and myocardial histology data will be transferred to a secured central database.
- Primary Outcome Measures
Name Time Method Changes in left ventricular longitudinal and circumferential strains Baseline to 3 and 6 months Changes in left ventricular longitudinal and circumferential strains will be measured using transthoracic echocardiography and segmental wall motion analysis with expected change \> 10%.
Change in quality of life questionnaire score Baseline to 3 and 6 months Change in quality of life KCCQ questionnaire score with expected decrease of ≥ 5 points
change in left ventricular ejection fraction (LVEF) Baseline to 6 months change in left ventricular ejection fraction (LVEF), measured by transthoracic echocardiography using Simpson's rule between the time of stem cell therapy and 6 months.
Changes in left ventricular end-systolic and end-diastolic dimensions Baseline to 3 and 6 months Changes in left ventricular end-systolic (LVESd) and end-diastolic dimensions (LVEDd) measured by transthoracic echocardiography in parasternal longitudinal axis with expected change \> 10%.
Changes in right ventricular size Baseline to 3 and 6 months Changes in right ventricular size (RVIDd) will be measured using transthoracic echocardiography with expected change \> 10%.
Change in 6-minute walk test Baseline to 3 and 6 months Change in 6-minute walk test with expected increase \> 30 m
Changes in serum markers of fibrosis and angiogenesis Baseline to 3 and 6 months Changes in serum markers of fibrosis and angiogenesis will be assessed by measuring biomarkers of fibrosis and angiogenesis using Luminex commercially available kits (Human XL Cytokine Luminex® Performance Assay 46-plex); any detectable change will be considered a positive response.
Change in serum neurohumoral activation Baseline to 3 and 6 months Change in serum neurohumoral activation will be assessed measuring NT-proBNP serum levels, with expected decrease \> 30%.
Change in heart failure-related hospitalization Baseline to 3 and 6 months Change in heart failure-related hospitalization; any decrease will be considered
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University Medical Center Ljubljana
🇸🇮Ljubljana, Slovenia