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

January 19, 2018 updated by: Bojan Vrtovec, University Medical Centre Ljubljana

Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
    • Please Select
      • Ljubljana, Please Select, Slovenia, 1000
        • UMC Ljubljana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group A
Repetitive stem cell administration
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.
Active Comparator: Group B
Single stem cell administration
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in left ventricular ejection fraction
Time Frame: baseline and 1 year
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in regional wall motion
Time Frame: baseline and 1 year
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
Change in left ventricular dimension
Time Frame: 1 year
The change in left ventricular dimensions between randomization and 1 year thereafter will be assessed by 2D echocardiography.
1 year
Change in exercise capacity
Time Frame: baseline and 1 year
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
Change in NT-proBNP
Time Frame: baseline and 1 year
baseline and 1 year

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Incidence of ventricular arrhythmias
Time Frame: 1 year
1 year
Cardiac mortality
Time Frame: 1 year
1 year
Hospitalization for heart failure
Time Frame: 1 year
1 year
Pump failure mortality
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Centre Ljubljana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 16, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 23, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REMEDIUM

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