Intra-coronary Versus Intramyocardial Application of Enriched CD133pos Autologous Bone Marrow Derived Stem Cells (AlsterMACS)
Primary Purpose
Heart Failure
Status
Terminated
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
autologous CD133pos stem cell application
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Chronic Ischemic Cardiomyopathy
Eligibility Criteria
Inclusion Criteria:
- Patients 18 to 80 years old
- Of female and male gender
- Patient has reduced ejection fraction as evaluated by routine clinical angiogram, echocardiography or MRI (≤45%) due to ischemic heart disease
- symptomatic heart failure NYHA ≥ II on optimal therapy
- coronary artery in the target region that can be used for cell infusion
- Patient has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent
Exclusion Criteria:
- planned or performed CABG surgery or PCI within 4 weeks of study entry
- recent myocardial infarction (< 6 months)
- TIMI flow < II in the coronary artery selected for infusion
- cardiogenic shock requiring mechanical ventilation or intra-aortic balloon pump
- progressive tumor disease
- primary disease of bone marrow including mal-function of components of the coagulation system
- women of child-bearing age premenopausal
- LV wall thickness < 5mm at planned site of injection
- ventricular wall thrombus
- severe aortic valvular heart disease
- severe atrial or ventricular tachycardia unresponsive to intravenous or oral drug therapy
- aneurysm of the anterior wall
- history of stroke
- know diseases of the liver resulting in reduced plasmatic coagulation with spontaneous INR >2
- patients with chronic infectious diseases (HBV, HCV, HIV, seropositivity for Treponema pallidum)
- patients taking part or have taken part in other clinical trials within the past 3 months
- patients unable to provide informed consent
- any other medical condition that the enrolling physician deems significant in representing a potential hazard for the patient when participating in this study
Sites / Locations
- ASKLEPIOS Klinik St. Georg
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
intra-coronary administration
intra-myocardial administration
Arm Description
Application of stem cells using the intra-coronary route.
Application of stem cells using the intra-myocardial route.
Outcomes
Primary Outcome Measures
LVEF
Improvement of global left ventricular function as well as global strain rate as assessed by echocardiography. Transthoracic echocardiography will be performed at baseline and after 6 and 12 month. Images are acquired in the standard parasternal and apical views.
Secondary Outcome Measures
Full Information
NCT ID
NCT01337011
First Posted
April 14, 2011
Last Updated
August 20, 2021
Sponsor
Asklepios proresearch
Collaborators
Miltenyi Biomedicine GmbH
1. Study Identification
Unique Protocol Identification Number
NCT01337011
Brief Title
Intra-coronary Versus Intramyocardial Application of Enriched CD133pos Autologous Bone Marrow Derived Stem Cells
Acronym
AlsterMACS
Official Title
Pilot Study Comparing the Effect of Intra-coronary Versus Intramyocardial Application of Enriched CD133pos Autologous Bone Marrow Derived Stem Cells for Improving Left Ventricular Function in Chronic Ischemic Cardiomyopathy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
study was stopped due to funding issues
Study Start Date
July 2011 (Actual)
Primary Completion Date
March 2, 2016 (Actual)
Study Completion Date
July 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Asklepios proresearch
Collaborators
Miltenyi Biomedicine GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a pilot study comparing the effect of intra-coronary versus intramyocardial application of enriched CD133pos autologous bone marrow derived stem cells for improving left ventricular function in chronic ischemic cardiomyopathy.
Detailed Description
Recent years have seen a tremendous improvement of possibilities to restore normal cardiac perfusion of the coronary arteries both by surgical and interventional techniques. In addition, several pharmacological approaches are available to block the mal-adaptive molecular signaling initiated by the Renin/Angiotensin/Aldosteron (RAAS) system. Device therapy achieving resychronisation has lowered morbidity and mortality. However, heart failure therapy still falls short to address the underlying disease of the heart muscle: loss of contractile force.
To achieve this aim and restore contractile force a regenerative approach is required. Early experimental studies suggested bone marrow cells to be able to differentiate towards functional cardiomyocytes when injected into the scar area after ischemic injury.2 These and other studies lead to clinical trials, where bone marrow cells were injected into the coronary circulation. Lately, the first completed multi-center, placebo-controlled, double-blinded study found several end points to be improved including global left ventricular function 3. At the same time genetically labelled experimental mouse models demonstrated differentiation of bone marrow cells towards a cardiomyocyte lineage to be a rare event,4 questioning at least the proposed molecular and cellular mechanism of intra-coronary cell therapy. Furthermore, several other clinical trials recently performed did either find no or a very limited effect of intra-coronary applied bone marrow cells. The effect appears to be related to improved angiogenesis. Our group has recently shown that in mammals endogenous regeneration of myocardium does occur after injury and can be enhanced via specific signaling pathways.5 Whether intra-coronary cell therapy is the ideal approach to enhance this process is currently unclear.
References:
Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, Hochadel M, Komajda M, Lassus J, Lopez-Sendon JL, Ponikowski P, Tavazzi L. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J. 2006;27:2725-2736.
Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A. 2001;98:10344-10349.
Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM, the R-AMII. Intracoronary Bone Marrow-Derived Progenitor Cells in Acute Myocardial Infarction. N Engl J Med. 2006;355:1210-1221.
Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664-668.
Zelarayan L, Noack C, Sekkali B, Kmecova J, Gehrke C, Renger A, Zafiriou MP, Nagel Rvd, Dietz R, Windt LJd, Balligand J-L, Bergmann MW. beta-catenin downregulation attenuates ischemic cardiac remodeling through enhanced resident precursor cell differentiation. Proc Natl Acad Sci U S A. 2008;105:19762-19767.
Krause KT, Jaquet K, Geidel S, Schneider C, Mandel C, Stoll HP, Hertting K, Harle T, Kuck KH. Percutaneous endocardial injection of erythropoietin: assessment of cardioprotection by electromechanical mapping. Eur J Heart Fail. 2006;8:443-450.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Chronic Ischemic Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Comparison of the effect of CD133pos. bone marrow derived stem cells using the intra-myocardial vs. the intra-coronary route of administration for improving left ventricular function in patients with chronic ischemic cardiomopathy.
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
intra-coronary administration
Arm Type
Experimental
Arm Description
Application of stem cells using the intra-coronary route.
Arm Title
intra-myocardial administration
Arm Type
Experimental
Arm Description
Application of stem cells using the intra-myocardial route.
Intervention Type
Other
Intervention Name(s)
autologous CD133pos stem cell application
Intervention Description
The study aims to show efficacy of both intra-myocardial autologous CD133pos bone marrow cell application as well as intra-coronary CD133pos cell application in patients with symptomatic ischemic heart disease. In addition, efficacy between the two delivery routes will be compared.
Primary Outcome Measure Information:
Title
LVEF
Description
Improvement of global left ventricular function as well as global strain rate as assessed by echocardiography. Transthoracic echocardiography will be performed at baseline and after 6 and 12 month. Images are acquired in the standard parasternal and apical views.
Time Frame
after 6 to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients 18 to 80 years old
Of female and male gender
Patient has reduced ejection fraction as evaluated by routine clinical angiogram, echocardiography or MRI (≤45%) due to ischemic heart disease
symptomatic heart failure NYHA ≥ II on optimal therapy
coronary artery in the target region that can be used for cell infusion
Patient has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent
Exclusion Criteria:
planned or performed CABG surgery or PCI within 4 weeks of study entry
recent myocardial infarction (< 6 months)
TIMI flow < II in the coronary artery selected for infusion
cardiogenic shock requiring mechanical ventilation or intra-aortic balloon pump
progressive tumor disease
primary disease of bone marrow including mal-function of components of the coagulation system
women of child-bearing age premenopausal
LV wall thickness < 5mm at planned site of injection
ventricular wall thrombus
severe aortic valvular heart disease
severe atrial or ventricular tachycardia unresponsive to intravenous or oral drug therapy
aneurysm of the anterior wall
history of stroke
know diseases of the liver resulting in reduced plasmatic coagulation with spontaneous INR >2
patients with chronic infectious diseases (HBV, HCV, HIV, seropositivity for Treponema pallidum)
patients taking part or have taken part in other clinical trials within the past 3 months
patients unable to provide informed consent
any other medical condition that the enrolling physician deems significant in representing a potential hazard for the patient when participating in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Bergmann, PD Dr.
Organizational Affiliation
Asklepios Kliniken Hamburg GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
ASKLEPIOS Klinik St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
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Intra-coronary Versus Intramyocardial Application of Enriched CD133pos Autologous Bone Marrow Derived Stem Cells
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