NCT02248532

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2014

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

September 16, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 25, 2014

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2017

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

January 23, 2018

Status Verified

January 1, 2018

Enrollment Period

3.7 years

First QC Date

September 16, 2014

Last Update Submit

January 19, 2018

Conditions

Dilated CardiomyopathyHeart Failure

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Changes in regional wall motion

    baseline and 1 year

  • Change in left ventricular dimension

    1 year

  • Change in exercise capacity

    baseline and 1 year

  • Change in NT-proBNP

    baseline and 1 year

Other Outcomes (4)

  • Incidence of ventricular arrhythmias

    1 year

  • Cardiac mortality

    1 year

  • Hospitalization for heart failure

    1 year

  • +1 more other outcomes

Study Arms (2)

Group A

ACTIVE COMPARATOR

Repetitive stem cell administration

Biological: Stem cell therapy

Group B

ACTIVE COMPARATOR

Single stem cell administration

Biological: Stem cell therapy

Interventions

Stem cell therapyBIOLOGICAL

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.

Group AGroup B

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UMC Ljubljana

Ljubljana, Please Select, 1000, Slovenia

Location

Related Publications (4)

  • 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.

    PMID: 24030420BACKGROUND

  • Vrtovec B, Poglajen G, Sever M, Zemljic G, Frljak S, Cerar A, Cukjati M, Jaklic M, Cernelc P, Haddad F, Wu JC. Effects of Repetitive Transendocardial CD34+ Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy. Circ Res. 2018 Jul 20;123(3):389-396. doi: 10.1161/CIRCRESAHA.117.312170. Epub 2018 Jun 7.

    PMID: 29880546DERIVED

  • Frljak S, Jaklic M, Zemljic G, Cerar A, Poglajen G, Vrtovec B. CD34+ Cell Transplantation Improves Right Ventricular Function in Patients with Nonischemic Dilated Cardiomyopathy. Stem Cells Transl Med. 2018 Feb;7(2):168-172. doi: 10.1002/sctm.17-0197.

    PMID: 29380563DERIVED

  • Rozman JZ, Perme MP, Jez M, Malicev E, Krasna M, Novakovic S, Vrtovec B, Rozman P. The effect of CD34+ cell telomere length and hTERT expression on the outcome of autologous CD34+ cell transplantation in patients with chronic heart failure. Mech Ageing Dev. 2017 Sep;166:42-47. doi: 10.1016/j.mad.2017.06.001. Epub 2017 Jun 19.

    PMID: 28636901DERIVED

MeSH Terms

Conditions

Cardiomyopathy, DilatedHeart Failure

Condition Hierarchy (Ancestors)

CardiomegalyHeart DiseasesCardiovascular DiseasesCardiomyopathiesLaminopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Director, Advanced Heart Failure and Transplantation

Study Record Dates

First Submitted

September 16, 2014

First Posted

September 25, 2014

Study Start

January 1, 2014

Primary Completion

September 1, 2017

Study Completion

December 1, 2017

Last Updated

January 23, 2018

Record last verified: 2018-01

Locations

SL(1)