Dilated CardiomyopathyPhase 2NCT00629018
Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
A Phase 2 study testing CD34+ autologous stem cell transplantation, Bone Marrow Stimulation and SC therapy in people with Dilated Cardiomyopathy, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
Several studies have documented that transplantation of bone marrow-derived cells (BMC) following acute myocardial infarction is associated with a reduction in infarct scar size and improvements in left ventricular function and perfusion. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Dilated Cardiomyopathy
- What is being tested?
- CD34+ autologous stem cell transplantation, Bone Marrow Stimulation and SC therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteSlovenia
- Study dates
- May 2006to Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Normal coronary angiogram
- Left ventricular ejection fraction < 40%
- NYHA III or IV heart failure symptoms
- Bone marrow reactivity (G-CSF test)
- Presence of viable myocardium
Who cannot join
- Hematologic malignancy
- Multiorgan failure
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Autologous Intracoronary Stem Cell Transplantation In Patients With End-Stage Dilated Cardiomyopathy
Several studies have documented that transplantation of bone marrow-derived cells (BMC) following acute myocardial infarction is associated with a reduction in infarct scar size and improvements in left ventricular function and perfusion. The available evidence in humans suggests that BMC transplantation is associated with improvements in physiologic and anatomic parameters in both acute myocardial infarction and chronic ischemic heart disease, above and beyond the conventional therapy. In particular, intracoronary application of BMC is proved to be safe and was associated with significant improvement in the left ventricular ejection fraction (LVEF) in patients with chronic heart failure.
In contrast to ischemic heart failure, the data on effects of BMC transplantation in patients with dilated cardiomyopathy are limited to pre-clinical studies. In a rat model of dilated cardiomyopathy, intramyocardial delivery of pluripotent mesenchymal cells improved LVEF, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis, suggesting that the beneficial effects of stem cell transplantation in dilated cardiomyopathy may primarily be related to their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors. Similarly, transplantation of cocultured mesenchymal stem cells and skeletal myoblasts was shown to improve LVEF in a murine model of Chagas disease.
Read more
Study Aim:
To define the clinical effects of BMC transplantation in dilated cardiomyopathy in a pilot clinical study investigating the effects of intracoronary CD34+ cell transplantation on functional, structural, neurohormonal, and electrophysiologic parameters in patients with end-stage dilated cardiomyopathy.
Read the detailed description
Patients were randomly allocated in a 1:1 ratio to receive intracoronary transplantation of autologous CD34+ stem cells (SC group) or no intracoronary infusion (control group). At the time of enrollment, and at yearly intervals thereafter, we performed detailed clinical evaluation, echocardiography, 6-minute walk test, and measured plasma levels of NT-proBNP. To better-define the potential role of inflammatory response, we also measured plasma inflammatory markers (tumor necrosis factor [TNF]-α and interleukin [IL]-6) at the time of CD34+ stem cell injection.
- Conditions
- Dilated Cardiomyopathy
- Being tested
- CD34+ autologous stem cell transplantation, Bone Marrow Stimulation, SC therapy
- Keywords
- Stem Cells, Heart Failure, Dilated Cardiomyopathy
- Medical subject headings
- Cardiomyopathy, Dilated, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34+ autologous stem cell transplantationBiological
Peripheral blood stem cells will be mobilized by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labeled with technetium. Patients will undergo myocardial perfusion scintigraphy for myocardial viability assessment and the collected CD34+ cells will be injected intracoronary in the artery supplying the segments of reduced tracer accumulation
Bone Marrow StimulationDrug
Also called G-CSF stimulation
Patients will undergo filgrastim stimulation and viability assessment using the same protocol as in Arm 1. However, in this group, no intracoronary stem cell delivery will be performed; the patients will receive placebo (saline).
SC therapyBiological
In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect
| Study group | Role | What they receive |
|---|---|---|
| SC Group | Experimental | SC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation':
In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect Receives: Biological: CD34+ autologous stem cell transplantation; Drug: Bone Marrow Stimulation; Biological: SC therapy |
| Controls | No intervention | Patients receiving no cell therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Failure Mortality
Measured: 5 years
Changes in Left Ventricular Ejection Fraction
Left ventricular ejection fraction measured by echocardiography
Measured: 5 years
Secondary outcomes (4)
Changes in Exercise Capacity
Measured: 5 years
Changes in Electrophysiologic Properties of Ventricular Myocardium
Measured: 6 months
Changes in Plasma Inflammatory Markers
Measured: 6 months
Changes in Left Ventricular Function
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2008 (estimated)
- Study startMay 2006
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- Blood Transfusion Centre of Slovenia, Stanford University
- Responsible party
- Principal investigator, Bojan Vrtovec, University Medical Centre Ljubljana
- Investigators
- Guillermo Torre Amione, MD, PhD, Study director, Methodist DeBakey Heart Center, Houston TX, USAFrancois Haddad, MD, Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00629018
- Sponsor's protocol ID
- DCM-SCT1
- Status last verified
- Apr 2015
- First submitted
- 25 Feb 2008
- Last updated
- 12 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Vrtovec B, Poglajen G, Sever M, Lezaic L, Domanovic D, Cernelc P, Haddad F, Torre-Amione G. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail. 2011 Apr;17(4):272-81. doi: 10.1016/j.cardfail.2010.11.007. Epub 2010 Dec 24.
PubMed 21440864
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Autologous Intracoronary Stem Cell Transplantation In Patients With End-Stage Dilated Cardiomyopathy
- ClinicalTrials.gov ID
- NCT00629018
- Acronym / sponsor ID
- DCM-SCT1
- Conditions
- Dilated Cardiomyopathy
- Keywords
- Stem Cells, Heart Failure, Dilated Cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- Blood Transfusion Centre of Slovenia, Stanford University
- Study start
- May 2006
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 5 Mar 2008 (estimated)
- Results
- Posted 12 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Several studies have documented that transplantation of bone marrow-derived cells (BMC) following acute myocardial infarction is associated with a reduction in infarct scar size and improvements in left ventricular function and perfusion. The available evidence in humans suggests that BMC transplantation is associated with improvements in physiologic and anatomic parameters in both acute myocardial infarction and chronic ischemic heart disease, above and beyond the conventional therapy. In particular, intracoronary application of BMC is proved to be safe and was associated with significant improvement in the left ventricular ejection fraction (LVEF) in patients with chronic heart failure.
In contrast to ischemic heart failure, the data on effects of BMC transplantation in patients with dilated cardiomyopathy are limited to pre-clinical studies. In a rat model of dilated cardiomyopathy, intramyocardial delivery of pluripotent mesenchymal cells improved LVEF, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis, suggesting that the beneficial effects of stem cell transplantation in dilated cardiomyopathy may primarily be related to their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors. Similarly, transplantation of cocultured mesenchymal stem cells and skeletal myoblasts was shown to improve LVEF in a murine model of Chagas disease.
Study Aim:
To define the clinical effects of BMC transplantation in dilated cardiomyopathy in a pilot clinical study investigating the effects of intracoronary CD34+ cell transplantation on functional, structural, neurohormonal, and electrophysiologic parameters in patients with end-stage dilated cardiomyopathy.
Detailed description
Patients were randomly allocated in a 1:1 ratio to receive intracoronary transplantation of autologous CD34+ stem cells (SC group) or no intracoronary infusion (control group). At the time of enrollment, and at yearly intervals thereafter, we performed detailed clinical evaluation, echocardiography, 6-minute walk test, and measured plasma levels of NT-proBNP. To better-define the potential role of inflammatory response, we also measured plasma inflammatory markers (tumor necrosis factor [TNF]-α and interleukin [IL]-6) at the time of CD34+ stem cell injection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SC Group | Experimental | Biological: CD34+ autologous stem cell transplantation, Drug: Bone Marrow Stimulation, Biological: SC therapySC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation': In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect |
| Controls | No intervention | –Patients receiving no cell therapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Normal coronary angiogram
- Left ventricular ejection fraction < 40%
- NYHA III or IV heart failure symptoms
- Bone marrow reactivity (G-CSF test)
- Presence of viable myocardium
Key exclusion criteria (2 listed)
- Hematologic malignancy
- Multiorgan failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD34+ autologous stem cell transplantationPeripheral blood stem cells will be mobilized by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labeled with technetium. Patients will undergo myocardial perfusion scintigraphy for myocardial viability assessment and the collected CD34+ cells will be injected intracoronary in the artery supplying the segments of reduced tracer accumulation | Biological | SC Group |
| Bone Marrow StimulationAlso: G-CSF stimulationPatients will undergo filgrastim stimulation and viability assessment using the same protocol as in Arm 1. However, in this group, no intracoronary stem cell delivery will be performed; the patients will receive placebo (saline). | Drug | SC Group |
| SC therapyIn the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect | Biological | SC Group |
Primary outcome
Heart Failure Mortality
Time frame: 5 years
Changes in Left Ventricular Ejection Fraction
Time frame: 5 years
Left ventricular ejection fraction measured by echocardiography
4 secondary outcomes
Changes in Exercise Capacity
Time frame: 5 years
Changes in Electrophysiologic Properties of Ventricular Myocardium
Time frame: 6 months
Changes in Plasma Inflammatory Markers
Time frame: 6 months
Changes in Left Ventricular Function
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21440864Vrtovec B, Poglajen G, Sever M, Lezaic L, Domanovic D, Cernelc P, Haddad F, Torre-Amione G. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail. 2011 Apr;17(4):272-81. doi: 10.1016/j.cardfail.2010.11.007. Epub 2010 Dec 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guillermo Torre Amione, MD, PhD study director
Methodist DeBakey Heart Center, Houston TX, USA
Francois Haddad, MD study director
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CD34+ autologous stem cell transplantation, Bone Marrow Stimulation and SC therapy in people with Dilated Cardiomyopathy, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart Failure Mortality (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00629018, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2015.