CELLpEF: Cell Therapy in HFpEF

Sponsor

University Medical Centre Ljubljana (Other)

Overall Status

Recruiting

CT.gov ID

NCT02923609

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Normal Ejection Fraction	Biological: Cell Therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

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).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).

Masking:

None (Open Label)

Masking Description:

The echocardiographer will be blinded for the timing of echocardiographic recordings.

Primary Purpose:

Treatment

Official Title:

A PILOT TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Actual Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Biological: 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.

Arm

Intervention/Treatment

Experimental: 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).

Biological: 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.

Outcome Measures

Primary Outcome Measures

Change in left ventricular filling pressures (E/e') assessed by echocardiography [Baseline, 6 months and 1 year]
The E/e' ratio will be calculated from early transmitral velocity divided by peak left ventricular relaxation velocity for estimation of the left ventricular filling pressure.

Secondary Outcome Measures

Change in exercise capacity [Baseline, 6 months and 1 year]
6-minute walk test will be performed by a blinded observer according to the standard protocol.
Change in NT-proBNP levels [Baseline, 6 months and 1 year]
NT-proBNP assays will be performed at a central independent laboratory, blinded to the patient's clinical data using a commercially available kit (Roche Diagnostics, Mannheim, Germany).
Change in systolic strain [Baseline, 6 months and 1 year]
Left ventricular longitudinal strains will be analyzed by speckle tracking echocardiography from apical four-chamber, two-chamber, and long-axis views.
Change in diastolic dysfunction grade [Baseline, 6 months and 1 year]
Diastolic dysfunction will be graded according based on E/A ratio and left atrial pressure estimation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Medical Center Ljubljana	Ljubljana		Slovenia	1000

Sponsors and Collaborators

University Medical Centre Ljubljana

Investigators

Principal Investigator: Bojan Vrtovec, MD, PhD, Department of Cardiology, UMC Ljubljana

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bojan Vrtovec, Medical Director, Advanced Heart Failure and Transplantation Programme, University Medical Centre Ljubljana

ClinicalTrials.gov Identifier:

NCT02923609

Other Study ID Numbers:

CELLpEF

First Posted:

Oct 4, 2016

Last Update Posted:

Feb 5, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Heart Failure

Study Results

No Results Posted as of Feb 5, 2021