Clinical trial NCT01660581: Intracardiac CD133+ Cells in Patients With No-option Resistant Angina
Official title: A Randomized,Prospective,Double-blind Study to Evaluate Intracardiac Injections of Bone Marrow,Autologous CD133+Cells(Electromechanical Mapping Based)in Patients With Resistant Angina and no Effective Revascularization Option. RegentVsel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stable Angina
Keywords: CD133+
stem cells
Coronary Artery Disease
Stable Angina Pectoris
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
First posted: 2012-08-08
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy of therapy with autological CD133+ cells in patients with angina resistant to pharmacological treatment and without the possibility of effective revascularization. Cells will be isolated from patients bone marrow and administered directly into the muscle of left ventricle. The main objective is to assess the treatments' influence on improvement of myocardial perfusion and function, and on decrease of occurrence of symptomatic angina.

Detailed description: Patients with a Stable angina pectoris (CCS II-IV) can potentially benefit from treatment with autological CD133+ cell populations, which include cells with a higher expression of cardiac and endothelial differentiation markers.

REGENT VSEL Trial will include Patients with Angina resistant to pharmacological treatment and without the possibility of effective revascularization.

The main objective of the study is to assess the treatments influence on:

* improvement of myocardial perfusion
* global and segmental contractility (LVEF)
* occurrence of symptomatic angina
* quality of life

Regent Vsel is a prospective, randomized, double blind, placebo-controlled study with a planned number of 60 Patients.

Randomization will be carried out according to a 1:1 mode. Every Patient will undergo a bone marrow aspiration. CD133+ cells will be isolated from bone marrow aspirates. Patients randomized to experimental group will receive isolated cells (direct left ventricular muscle administration). Patients enrolled to control group will get only a placebo solution injected into the muscle.

Eligibility criteria: Inclusion Criteria:

1. Stable angina CCS II-IV despite maximum pharmacotherapy for at least 2 weeks since last medications change
2. Presence of ≥ 1 myocardial segment with ischemia features in Tc-99m SPECT
3. Patients disqualified from revascularization procedures by Heart Team
4. Patient age \> 18 and \< 75 year old
5. Patient must provide written informed consent for participation in study

Exclusion Criteria:

1. Acute coronary syndrome in less than 6 months prior to enrollment
2. Heart failure NYHA III-IV
3. LVEF \<35%
4. Presence of intracardiac thrombus (echocardiography confirmed), massive calcification of the aortic valve and left ventricular aneurysm
5. Previous cardioverter-defibrillator or cardiac stimulator implantation
6. Allergy to contrast agents
7. History of malignancy
8. HIV, HBV, HCV infection
9. Life expectancy less than 6 months
10. Bleeding diathesis
11. Renal insufficiency (GFR \< 30 mL/min/1.73m2)
12. Pregnancy, lactation, or ineffective contraception in women of childbearing potential

Primary outcomes:
measure: Myocardial perfusion change
timeFrame: 4 months after application of cell therapy
Secondary outcomes:
measure: Global and segmental contractility change and myocardial perfusion change
timeFrame: MRI 4 months and echocardiography 4 and 12 months after application of cell therapy
measure: Exercise tolerance
timeFrame: 4 and 12 months after application of cell therapy
measure: Occurrence of symptomatic angina
timeFrame: 1, 4, 6 and 12 months after application of cell therapy
measure: Quality of life
timeFrame: 1, 4, 6 and 12 months after application of cell therapy
measure: Occurrence of ventricular arrhythmia
timeFrame: 1, 4, 6 and 12 months after application of cell therapy
measure: Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments
timeFrame: 4 months after application of cell therapy
Other outcomes:
Locations:
city: Katowice-Ochojec
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca
state: Silesian
Study officials:
affiliation: Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne III Klinika Kardiologii
name: Wojciech Wojakowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007 May 28;167(10):989-97. doi: 10.1001/archinte.167.10.989.
citation: Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, Vanderheyden M, Kim HS, Kang HJ, Strauer BE, Vetrovec GW. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol. 2007 Oct 30;50(18):1761-7. doi: 10.1016/j.jacc.2007.07.041. Epub 2007 Oct 15.
citation: Wojakowski W, Tendera M, Zebzda A, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Krol M, Ochala A, Kozakiewicz K, Ratajczak MZ. Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction. Eur Heart J. 2006 Feb;27(3):283-9. doi: 10.1093/eurheartj/ehi628. Epub 2005 Nov 2.
citation: Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004 Nov 16;110(20):3213-20. doi: 10.1161/01.CIR.0000147609.39780.02. Epub 2004 Nov 8.
citation: van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009 May 20;301(19):1997-2004. doi: 10.1001/jama.2009.685.
citation: Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. doi: 10.1161/ATVBAHA.107.155317. Epub 2007 Oct 19.
citation: Wojakowski W, Jadczyk T, Michalewska-Wludarczyk A, Parma Z, Markiewicz M, Rychlik W, Kostkiewicz M, Gruszczynska K, Blach A, Dzier Zak-Mietla M, Wanha W, Ciosek J, Ochala B, Rzeszutko L, Cybulski W, Partyka L, Zasada W, Wludarczyk W, Dworowy S, Kuczmik W, Smolka G, Pawlowski T, Ochala A, Tendera M. Effects of Transendocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial. Circ Res. 2017 Feb 17;120(4):670-680. doi: 10.1161/CIRCRESAHA.116.309009. Epub 2016 Nov 30.