The Effects of Cell Therapy on Myocardial Recovery in Chronic Heart Failure Patients Undergoing Left Ventricular Assist Device Support: A Pilot Trial (CELL-VAD Pilot)

University Medical Centre Ljubljana1 个研究点分布在 1 个国家目标入组 10 人开始时间: 2022年5月1日最近更新: 2026年1月26日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方: University Medical Centre Ljubljana
入组人数: 10
试验地点: 1
主要终点: Changes in left ventricular longitudinal and circumferential strains

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

盲法说明

Imaging core lab employees will be blinded to the patient's status (before or after cell therapy)

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patient inclusion criteria will consist of all of the following:
•non-ischemic dilated cardiomyopathy
•patient accepted for LVAD support
•optimal (or maximal tolerable therapy) heart failure ≥ 2 months
•age 18-65 years
•ability to provide informed consent

排除标准

•will consist of any of the following:
•ischemic cardiomyopathy
•Cardiomyopathy with a reversible cause that has not been treated e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity & chronic uncontrolled tachycardia.
•Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy.
•ongoing or recent (less than 1 month) infection
•acute multi-organ failure
•clinically significant anemia (Hb < 10 g/dL)
•clinically significant leukopenia (L < 2 x 109/L) or leukocytosis (L > 14 x 109/L)
•clinically significant thrombocytopenia (TRC < 50 x 109/L)
•known disorders of hemostasis that can not be corrected
•history of any thromboembolic complications
•chronic kidney disease (higher than stage III)
•chronic liver disease (Child B or C)
•diminished functional capacity for other reasons such as COPD, moderate or severe claudications, severe musculosceletal system pain or morbid obesity (BMI > 35 kg/m2)
•aortic stenosis (AVA < 1.3 cm2) or ocluded aortic valve
•artificial (mechanical or biological) aortic valve
•patients with reduced immune response
•history of limphoprolipherative disorders or malignancy within 5 years
•left ventricular thrombus
•participation in another interventional clinical trial
•life expectancy less than 12 months
•known hypersensitivity to DMSO, penicillin or streptomycin

研究组 & 干预措施

Treatment Arm

Experimental

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.

干预措施: CD34+ stem cell therapy (Biological)