Intracardiac CD133+ Cells in Patients With No-option Resistant Angina (RegentVsel)

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

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.

Study Overview

• Status: Completed
• Conditions: Stable Angina
• Intervention / Treatment: Biological: intramyocardial injection (electromechanical mapping based); Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Silesian
    • Katowice-Ochojec, Silesian, Poland, 40-635
      • Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD133+; intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow	Biological: intramyocardial injection (electromechanical mapping based); Patient will undergo 3D electric and mechanical intracardiac mapping; based on maps generated intramyocardial administration of autologous CD133+ cells or placebo will be performed.
Placebo Comparator: Placebo; intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum	Biological: Placebo; Patients in the placebo group receive 0.9% NaCl solution with 0.5% solution of the patient's own serum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial perfusion change	Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT)	4 months after application of cell therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	MRI 4 months and echocardiography 4 and 12 months after application of cell therapy
Exercise tolerance	Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA)	4 and 12 months after application of cell therapy
Occurrence of symptomatic angina	CCS, nitrates usage	1, 4, 6 and 12 months after application of cell therapy
Quality of life	Quality of life assessed by standard questionnaires: SF37, Seattle Angina	1, 4, 6 and 12 months after application of cell therapy
Occurrence of ventricular arrhythmia	24 hrs ECG monitoring	1, 4, 6 and 12 months after application of cell therapy
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	4 months after application of cell therapy

Collaborators and Investigators

• Sponsor: Medical University of Silesia
• Investigators: Principal Investigator: Wojciech Wojakowski, MD, PhD, Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne III Klinika Kardiologii

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 7, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Actual): September 28, 2017
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; stem cells; CD133+; Stable Angina Pectoris
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: Regent Vsel; 2011-005435-98 (EudraCT Number)