Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT01337011 |
| Other study ID # |
1884 |
| Secondary ID |
2009-013103-63 |
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2011 |
| Est. completion date |
July 17, 2017 |
Study information
| Verified date |
August 2021 |
| Source |
Asklepios proresearch |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
