Cell Therapy and Myocardial Recovery in Heart Failure Patients Undergoing Left Ventricular Assist Device Support

NCT ID: NCT06154044

Last Updated: 2023-12-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2025-05-31

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.

Conditions

Heart Failure; Mechanical Circulatory Support

Keywords

heart failure; mechanical circulatory support; stem cells

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

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.

Group Type: EXPERIMENTAL

CD34+ stem cell therapy

Intervention Type: BIOLOGICAL

After 5-days GCSF stimulation all patients will undergo apheresis to obtain CD34+ cell which will subsequently be injected in the target coronary artery using microcatheter.

Interventions

CD34+ stem cell therapy

After 5-days GCSF stimulation all patients will undergo apheresis to obtain CD34+ cell which will subsequently be injected in the target coronary artery using microcatheter.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. non-ischemic dilated cardiomyopathy

2. patient accepted for LVAD support

3. optimal (or maximal tolerable therapy) heart failure ≥ 2 months

4. age 18-65 years

5. ability to provide informed consent

Exclusion Criteria

1. ischemic cardiomyopathy

2. 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.

3. Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy.

4. ongoing or recent (less than 1 month) infection

5. acute multi-organ failure

6. clinically significant anemia (Hb < 10 g/dL)

7. clinically significant leukopenia (L < 2 x 109/L) or leukocytosis (L > 14 x 109/L)

8. clinically significant thrombocytopenia (TRC < 50 x 109/L)

9. known disorders of hemostasis that can not be corrected

10. history of any thromboembolic complications

11. chronic kidney disease (higher than stage III)

12. chronic liver disease (Child B or C)

13. diminished functional capacity for other reasons such as COPD, moderate or severe claudications, severe musculosceletal system pain or morbid obesity (BMI > 35 kg/m2)

14. aortic stenosis (AVA < 1.3 cm2) or ocluded aortic valve

15. artificial (mechanical or biological) aortic valve

16. patients with reduced immune response

17. history of limphoprolipherative disorders or malignancy within 5 years

18. left ventricular thrombus

19. participation in another interventional clinical trial

20. life expectancy less than 12 months

21. known hypersensitivity to DMSO, penicillin or streptomycin

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bojan Vrtovec, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Ljubljana

Locations

University Medical Center Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Mateja Lani

Role: CONTACT

Phone: +38615221163

Email: mateja.lani@kclj.si

Gregor Poglajen, MD, PhD

Role: CONTACT

Phone: +38615228671

Email: gregor.poglajen@kclj.si

Facility Contacts

Bojan Vrtovec, MD, PhD

Role: primary

Gregor Poglajen, MD, PhD

Role: backup

Other Identifiers

UMC 1

Identifier Type: -

Identifier Source: org_study_id