Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy (REMEDIUM)

Heart Failure Clinical Trial

— REMEDIUM  

Official title:

Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02248532
• Other study ID #: REMEDIUM
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 16, 2014
• Last updated: January 19, 2018
• Start date: January 2014
• Est. completion date: December 2017

Study information

• Verified date: January 2018
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of REMEDIUM project is to develop personalized stem cell therapy for patients with chronic heart failure due to dilated cardiomyopathy (DCM). The main focus of the project is (1) on repetitive administration of cell therapy that would allow for long-lasting improvements in heart function and outcome in this patient population. In parallel, the investigators aim to (2) develop a standardized patient-specific stem cell product that could be cryopreserved and stored in a stem cell bank for prolonged time periods, and used for therapeutic application when clinically indicated. By using a unique multimodality imaging platform, the goal of this project is also to (3) define standardized clinical criteria that would serve as a guideline for evaluation of the effects of stem cell therapy in future clinical trials and everyday clinical settings. Finally, to improve the clinical implementation of cell therapy,the investigators aim to (4) develop a stem cell delivery technique that could be used to treat both left and right and ventricular failure and could be implemented in a standardized fashion designed for a widespread clinical use.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 18-70 years old

• Diagnosis of DCM according to European Society of Cardiology position statement

• Left ventricular ejection fraction (LVEF) by echocardiography 20-40%,

• New York Heart Association (NYHA) functional class heart failure II or III for at least 3 months before referral.

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy
• Heart Failure

Intervention

Biological:
• Stem cell therapy
Bone marrow cells will be mobilized into peripheral blood by daily subcutaneous injections of G-CSF (10 µg/kg daily) and collected by leukapheresis. Positive immunomagnetic selection of CD34+ cells will be performed. Electroanatomic mapping of the left ventricle will be performed using the Biosense NOGA system (Biosense-Webster®, Diamond Bar, CA). The target area for cell delivery will be defined as the myocardial segments with unipolar voltage potentials =8.3 mV, bipolar amplitudes >1.9 mV, and linear shortening <6%. Intramyocardial delivery of cell suspension will be performed with the MyoStar (BiosenseWebster®, Diamond Bar, CA) injection catheter. Each patient will receive 20 injections (0.3 mL each; total volume of 6 mL). All the procedures will be repeated 6 months after baseline.

Locations

Country	Name	City	State
Slovenia	UMC Ljubljana	Ljubljana	Please Select

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (1)

Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013 Sep 10;128(11 Suppl 1):S42-9. doi: 10.1161/CIRCULATIONAHA.112.000230. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of ventricular arrhythmias		1 year
Other	Cardiac mortality		1 year
Other	Hospitalization for heart failure		1 year
Other	Pump failure mortality		1 year
Primary	Change in left ventricular ejection fraction	The echocardiography data will be recorded and analyzed at the end of the study by an independent echocardiographer who will be blinded to the patient's treatment status and the timing of the recordings. Left ventricular end-systolic volume and end-diastolic volume and LVEF will be estimated using the Simpson's biplane method and left ventricular end-systolic dimension and end-diastolic dimension will be measured in the parasternal long axis view. All echocardiographic measurements will be averaged for 5 cycles.. The change in left ventricular ejection fraction (LVEF) between randomization and 1 year thereafter will be assessed by 2D echocardiography.	baseline and 1 year
Secondary	Changes in regional wall motion	Left ventricular segmental wall motion analysis (strain) will be evaluated with TomTec software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany), using a 17-segment model of the left ventricle.	baseline and 1 year
Secondary	Change in left ventricular dimension	The change in left ventricular dimensions between randomization and 1 year thereafter will be assessed by 2D echocardiography.	1 year
Secondary	Change in exercise capacity	Change in exercise capacity will be evaluated by 6-minute walk test was performed by a blinded observer according to the standard protocol.	baseline and 1 year
Secondary	Change in NT-proBNP		baseline and 1 year