Cell Therapy in HFpEF

NCT02923609 | Completed Phase 2

• 1 other identifier: CELLpEF
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure With Normal Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular filling pressures (E/e') assessed by echocardiography

  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.

  Baseline, 6 months and 1 year

Secondary Outcomes (4)

• Change in exercise capacity

  Baseline, 6 months and 1 year

• Change in NT-proBNP levels

  Baseline, 6 months and 1 year

• Change in systolic strain

  Baseline, 6 months and 1 year

• Change in diastolic dysfunction grade

  Baseline, 6 months and 1 year

Study Arms (1)

SC Group

EXPERIMENTAL

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

Interventions

Cell Therapy 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.

SC Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Center Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (1)

• 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.

  PMID: 35775390 DERIVED

MeSH Terms

Interventions

Cell- and Tissue-Based Therapy

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Bojan Vrtovec, MD, PhD

  Department of Cardiology, UMC Ljubljana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: The echocardiographer will be blinded for the timing of echocardiographic recordings.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Advanced Heart Failure and Transplantation Programme

Model Details: 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).

Study Record Dates

• First Submitted: October 3, 2016
• First Posted: October 4, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2022
• Study Completion: March 1, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)