Cell Therapy in HFpEF

NCT ID: NCT02923609

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2022-03-31

Brief 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.

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.

Conditions

Heart Failure With Normal Ejection Fraction

Study Design

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

Study Groups

SC Group

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).

Group Type: EXPERIMENTAL

Cell Therapy

Intervention Type: BIOLOGICAL

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.

Interventions

Cell Therapy

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Bojan Vrtovec

Medical Director, Advanced Heart Failure and Transplantation Programme

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bojan Vrtovec, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, UMC Ljubljana

Locations

University Medical Center Ljubljana

Ljubljana, , Slovenia

Countries

Slovenia

References

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.

Reference Type: DERIVED

PMID: 35775390 (View on PubMed)

Other Identifiers

CELLpEF

Identifier Type: -

Identifier Source: org_study_id