Intracardiac CD133+ Cells in Patients With No-option Resistant Angina (RegentVsel)
Primary Purpose
Stable Angina
Status
Completed
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
intramyocardial injection (electromechanical mapping based)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Stable Angina focused on measuring CD133+, stem cells, Coronary Artery Disease, Stable Angina Pectoris
Eligibility Criteria
Inclusion Criteria:
- Stable angina CCS II-IV despite maximum pharmacotherapy for at least 2 weeks since last medications change
- Presence of ≥ 1 myocardial segment with ischemia features in Tc-99m SPECT
- Patients disqualified from revascularization procedures by Heart Team
- Patient age > 18 and < 75 year old
- Patient must provide written informed consent for participation in study
Exclusion Criteria:
- Acute coronary syndrome in less than 6 months prior to enrollment
- Heart failure NYHA III-IV
- LVEF <35%
- Presence of intracardiac thrombus (echocardiography confirmed), massive calcification of the aortic valve and left ventricular aneurysm
- Previous cardioverter-defibrillator or cardiac stimulator implantation
- Allergy to contrast agents
- History of malignancy
- HIV, HBV, HCV infection
- Life expectancy less than 6 months
- Bleeding diathesis
- Renal insufficiency (GFR < 30 mL/min/1.73m2)
- Pregnancy, lactation, or ineffective contraception in women of childbearing potential
Sites / Locations
- Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CD133+
Placebo
Arm Description
intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow
intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum
Outcomes
Primary Outcome Measures
Myocardial perfusion change
Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT)
Secondary Outcome Measures
Global and segmental contractility change and myocardial perfusion change
Global and segmental contractility change and myocardial perfusion change assessed by magnetic resonance imaging with adenosine administration, and echocardiography with contrast
Exercise tolerance
Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA)
Occurrence of symptomatic angina
CCS, nitrates usage
Quality of life
Quality of life assessed by standard questionnaires: SF37, Seattle Angina
Occurrence of ventricular arrhythmia
24 hrs ECG monitoring
Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments
Assessed by Intravascular Ultrasound (IVUS) and Optical coherence tomography (OCT) examination
Full Information
NCT ID
NCT01660581
First Posted
August 6, 2012
Last Updated
September 27, 2017
Sponsor
Medical University of Silesia
1. Study Identification
Unique Protocol Identification Number
NCT01660581
Brief Title
Intracardiac CD133+ Cells in Patients With No-option Resistant Angina
Acronym
RegentVsel
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
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Silesia
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stable Angina
Keywords
CD133+, stem cells, Coronary Artery Disease, Stable Angina Pectoris
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CD133+
Arm Type
Experimental
Arm Description
intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum
Intervention Type
Biological
Intervention Name(s)
intramyocardial injection (electromechanical mapping based)
Intervention Description
Patient will undergo 3D electric and mechanical intracardiac mapping; based on maps generated intramyocardial administration of autologous CD133+ cells or placebo will be performed.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Patients in the placebo group receive 0.9% NaCl solution with 0.5% solution of the patient's own serum.
Primary Outcome Measure Information:
Title
Myocardial perfusion change
Description
Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT)
Time Frame
4 months after application of cell therapy
Secondary Outcome Measure Information:
Title
Global and segmental contractility change and myocardial perfusion change
Description
Global and segmental contractility change and myocardial perfusion change assessed by magnetic resonance imaging with adenosine administration, and echocardiography with contrast
Time Frame
MRI 4 months and echocardiography 4 and 12 months after application of cell therapy
Title
Exercise tolerance
Description
Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA)
Time Frame
4 and 12 months after application of cell therapy
Title
Occurrence of symptomatic angina
Description
CCS, nitrates usage
Time Frame
1, 4, 6 and 12 months after application of cell therapy
Title
Quality of life
Description
Quality of life assessed by standard questionnaires: SF37, Seattle Angina
Time Frame
1, 4, 6 and 12 months after application of cell therapy
Title
Occurrence of ventricular arrhythmia
Description
24 hrs ECG monitoring
Time Frame
1, 4, 6 and 12 months after application of cell therapy
Title
Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments
Description
Assessed by Intravascular Ultrasound (IVUS) and Optical coherence tomography (OCT) examination
Time Frame
4 months after application of cell therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Stable angina CCS II-IV despite maximum pharmacotherapy for at least 2 weeks since last medications change
Presence of ≥ 1 myocardial segment with ischemia features in Tc-99m SPECT
Patients disqualified from revascularization procedures by Heart Team
Patient age > 18 and < 75 year old
Patient must provide written informed consent for participation in study
Exclusion Criteria:
Acute coronary syndrome in less than 6 months prior to enrollment
Heart failure NYHA III-IV
LVEF <35%
Presence of intracardiac thrombus (echocardiography confirmed), massive calcification of the aortic valve and left ventricular aneurysm
Previous cardioverter-defibrillator or cardiac stimulator implantation
Allergy to contrast agents
History of malignancy
HIV, HBV, HCV infection
Life expectancy less than 6 months
Bleeding diathesis
Renal insufficiency (GFR < 30 mL/min/1.73m2)
Pregnancy, lactation, or ineffective contraception in women of childbearing potential
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wojciech Wojakowski, MD, PhD
Organizational Affiliation
Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne III Klinika Kardiologii
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca
City
Katowice-Ochojec
State/Province
Silesian
ZIP/Postal Code
40-635
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
17533201
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.
Results Reference
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PubMed Identifier
17964040
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.
Results Reference
background
PubMed Identifier
16267071
Citation
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Results Reference
background
PubMed Identifier
15533859
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.
Results Reference
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PubMed Identifier
19454638
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.
Results Reference
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PubMed Identifier
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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.
Results Reference
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PubMed Identifier
27903568
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.
Results Reference
derived
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Intracardiac CD133+ Cells in Patients With No-option Resistant Angina
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