Clinical trial NCT02923609: Cell Therapy in HFpEF
Official title: A PILOT TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Normal Ejection Fraction
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2016-10-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The study is designed in a prospective crossover fashion. In Phase 1 of the study, all patients are treated with optimization of medical therapy for 6 months. Thereafter, all patients cross over to Phase 2 of the study, where they receive transendocardial CD34+ cell therapy. Follow-up of Phase 2 lasts 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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in left ventricular filling pressures (E/e') assessed by echocardiography
timeFrame: Baseline, 6 months and 1 year
Secondary outcomes:
measure: Change in exercise capacity
timeFrame: Baseline, 6 months and 1 year
measure: Change in NT-proBNP levels
timeFrame: Baseline, 6 months and 1 year
measure: Change in systolic strain
timeFrame: Baseline, 6 months and 1 year
measure: Change in diastolic dysfunction grade
timeFrame: Baseline, 6 months and 1 year
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Center Ljubljana
Study officials:
affiliation: Department of Cardiology, UMC Ljubljana
name: Bojan Vrtovec, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.