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Stem Cell Study for Patients With Heart Disease

Primary Purpose

Chest Pain, Chronic Myocardial Ischemia, Coronary Artery Disease

Status
Terminated
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Autologous peripheral blood CD34 positive cell therapy
Sponsored by
Foundation for Biomedical Research and Innovation
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chest Pain focused on measuring Angina, Heart diseases, Pain, Vascular diseases

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: -Chronic severe CAD patients fulfilling all the following criteria are considered suitable for inclusion in the study. At least 6 months since last episode of myocardial infarction or at least 3 months since initial anginal episode. Patients fulfilling either of the following criteria based on the extent of CAD by coronary angiography and LVEF by echocardiography. Patients with single vessel CAD and LVEF < 50% Patients with multivessel CAD Reversible myocardial ischemia as revealed by sestamibi SPECT stress myocardial scintigraphy. Patients for whom angioplasty and bypass are not indicated because of anatomical or procedural reasons or frequent reocclusion/restenosis following traditional revascularization. Age is between 20 and 80 (at time of consent). Exercise tolerance time (ETT) duration ≥ 3 minutes and < 13 minutes on a modified Bruce protocol on 2 consecutive tests (> 24 hours but < 2 weeks apart), with the difference between the 2 exercise times within 25% of their mean (Patients should not be informed of exercise restrictions required for entry into the study). Patients who can give informed consent themselves in writing. Exclusion Criteria: Any one of the following exclusion criteria is sufficient to disqualify a patient from the study. Sustained ventricular tachycardia in a 24-hour ECG. Chronic atrial fibrillation. Less than 6 months since last episode of cerebral infarction. Less than 6 months since last coronary angioplasty or less than 3 months since last bypass surgery. Patients with unstable angina, with a treatment rating of 3 in the Braunwald system (refer to 5.4.), but a severity of III and a clinical rating of B or C. Presence of left ventricular thrombus by echocardiography Patients with a malignant tumor*. Patients with diabetic proliferating retinopathy** (new Fukuda classification BI to BV). Patients with chronic rheumatoid arthritis. Patients with a history of severe allergic reactions or side effects to G-CSF preparations or apheresis. Patients with hematological disease (leukemia, myeloproliferative disease, or myelodysplastic syndromes). Patients currently suffering from or having a history of interstitial pneumonitis. Patients for whom cranial MRA reveals cerebral aneurysm. Patients for whom abdominal CT or ultrasonography reveals splenomegaly. Patients with cirrhosis of the liver. Patients who cannot discontinue Warfarin. Leukocytes less than 4,000/µL or exceeding 10,000/µL. Platelets less than 100,000/µL. Hemoglobin less than 10 g/dL. AST (GOT) exceeding 100 IU/L or ALT (GPT) exceeding 100 IU/L. Patients for whom it is impossible to perform both cardiac MRI and left ventriculography (LVG) (see 9.2.4 for cardiac MRI details and 9.2.9 for LVG details). Patients with gate disturbance for reasons other than CAD (such as critical limb ischemia, sciatic neuralgia, or vasculitis), making exercise tolerance evaluation on a treadmill with stress ECG difficult. Pregnant or nursing patients, those who may be pregnant, or those who plan on becoming pregnant before the end of the study period. Any other reason that the Clinical Supervisors or Clinical Researchers may have for considering a case unsuitable for the study.

Sites / Locations

  • Kobe Institute of Biomedical Research and Innovation
  • Kobe City General Hospital
  • Okayama University School of Medicine

Outcomes

Primary Outcome Measures

Efficacy: Severity of myocardial perfusion abnormality by sestamibi SPECT stress myocardial scintigraphy
Safety: Severe adverse events within 4 weeks after cell therapy

Secondary Outcome Measures

CCSAS (Canada Cardiovascular Society Anginal Score)
NYHA (New York Heart Association) classification
Exercise tolerance by treadmill
Left ventricular function by cardiac MRI

Full Information

First Posted
September 13, 2005
Last Updated
June 21, 2011
Sponsor
Foundation for Biomedical Research and Innovation
Collaborators
Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan, Kobe City General Hospital, Okayama University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00221182
Brief Title
Stem Cell Study for Patients With Heart Disease
Official Title
Phase I / II Clinical Trial Regarding Vascular Regeneration Therapy by Transplantation of Autologous Peripheral Blood Endothelial Progenitor Cells (CD34+ Cells) in No-Option Patients With Chronic Myocardial Ischemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Terminated
Why Stopped
slow recruitment of the study subjects
Study Start Date
September 2005 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Foundation for Biomedical Research and Innovation
Collaborators
Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan, Kobe City General Hospital, Okayama University School of Medicine

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine if stem cell therapy with your own cells (autologous cells) delivered with a catheter to regions of the heart with poor blood flow will be safe and if it will relieve your chest pain, increase the blood flow, and/or improve the cardiac contractility (function) by regenerating blood vessels in your heart.
Detailed Description
Chronic myocardial ischemia (MI) is a progressive disease, which arises as a result of atherosclerosis in coronary arteries. Prognosis of chronic MI is poor, and no effective treatments have been established in patients who are not eligible for the traditional revascularization therapies such as angioplasty and bypass procedures due to the inappropriate anatomy of the coronary arteries or frequent reocclusion following revascularization. Therefore, it is necessary to establish novel revascularization treatment to improve prognosis of the no-option patients. We will study the safety and clinical efficiency of vascular regeneration by means of transplantation of autologous peripheral blood endothelial progenitor cells (CD34 positive cells) in patients with severe chronic coronary artery disease (CAD) who are not eligible for traditional revascularization treatments. The primary endpoint is the severity of myocardial ischemia identified by sestamibi SPECT stress myocardial scintigraphy and the evaluation of adverse effect rates, while the secondary endpoints are evaluation of CCSAS and NYHA classification, regional myocardial blood flow as revealed by PET scan, and various left ventricular function indices.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chest Pain, Chronic Myocardial Ischemia, Coronary Artery Disease, Angina, Myocardial Infarction
Keywords
Angina, Heart diseases, Pain, Vascular diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Genetic
Intervention Name(s)
Autologous peripheral blood CD34 positive cell therapy
Primary Outcome Measure Information:
Title
Efficacy: Severity of myocardial perfusion abnormality by sestamibi SPECT stress myocardial scintigraphy
Title
Safety: Severe adverse events within 4 weeks after cell therapy
Secondary Outcome Measure Information:
Title
CCSAS (Canada Cardiovascular Society Anginal Score)
Title
NYHA (New York Heart Association) classification
Title
Exercise tolerance by treadmill
Title
Left ventricular function by cardiac MRI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: -Chronic severe CAD patients fulfilling all the following criteria are considered suitable for inclusion in the study. At least 6 months since last episode of myocardial infarction or at least 3 months since initial anginal episode. Patients fulfilling either of the following criteria based on the extent of CAD by coronary angiography and LVEF by echocardiography. Patients with single vessel CAD and LVEF < 50% Patients with multivessel CAD Reversible myocardial ischemia as revealed by sestamibi SPECT stress myocardial scintigraphy. Patients for whom angioplasty and bypass are not indicated because of anatomical or procedural reasons or frequent reocclusion/restenosis following traditional revascularization. Age is between 20 and 80 (at time of consent). Exercise tolerance time (ETT) duration ≥ 3 minutes and < 13 minutes on a modified Bruce protocol on 2 consecutive tests (> 24 hours but < 2 weeks apart), with the difference between the 2 exercise times within 25% of their mean (Patients should not be informed of exercise restrictions required for entry into the study). Patients who can give informed consent themselves in writing. Exclusion Criteria: Any one of the following exclusion criteria is sufficient to disqualify a patient from the study. Sustained ventricular tachycardia in a 24-hour ECG. Chronic atrial fibrillation. Less than 6 months since last episode of cerebral infarction. Less than 6 months since last coronary angioplasty or less than 3 months since last bypass surgery. Patients with unstable angina, with a treatment rating of 3 in the Braunwald system (refer to 5.4.), but a severity of III and a clinical rating of B or C. Presence of left ventricular thrombus by echocardiography Patients with a malignant tumor*. Patients with diabetic proliferating retinopathy** (new Fukuda classification BI to BV). Patients with chronic rheumatoid arthritis. Patients with a history of severe allergic reactions or side effects to G-CSF preparations or apheresis. Patients with hematological disease (leukemia, myeloproliferative disease, or myelodysplastic syndromes). Patients currently suffering from or having a history of interstitial pneumonitis. Patients for whom cranial MRA reveals cerebral aneurysm. Patients for whom abdominal CT or ultrasonography reveals splenomegaly. Patients with cirrhosis of the liver. Patients who cannot discontinue Warfarin. Leukocytes less than 4,000/µL or exceeding 10,000/µL. Platelets less than 100,000/µL. Hemoglobin less than 10 g/dL. AST (GOT) exceeding 100 IU/L or ALT (GPT) exceeding 100 IU/L. Patients for whom it is impossible to perform both cardiac MRI and left ventriculography (LVG) (see 9.2.4 for cardiac MRI details and 9.2.9 for LVG details). Patients with gate disturbance for reasons other than CAD (such as critical limb ischemia, sciatic neuralgia, or vasculitis), making exercise tolerance evaluation on a treadmill with stress ECG difficult. Pregnant or nursing patients, those who may be pregnant, or those who plan on becoming pregnant before the end of the study period. Any other reason that the Clinical Supervisors or Clinical Researchers may have for considering a case unsuitable for the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takayuki Asahara, M.D.
Organizational Affiliation
Foundation for Biomedical Research and Innovation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kobe Institute of Biomedical Research and Innovation
City
Kobe
State/Province
Hyogo-Pref.
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Kobe City General Hospital
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Okayama University School of Medicine
City
Okayama
ZIP/Postal Code
700-8530
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
15308462
Citation
Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol. 2004 Sep;287(3):C572-9. doi: 10.1152/ajpcell.00330.2003.
Results Reference
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PubMed Identifier
12551872
Citation
Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation. 2003 Jan 28;107(3):461-8. doi: 10.1161/01.cir.0000046450.89986.50.
Results Reference
background
PubMed Identifier
11156872
Citation
Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001 Feb 6;103(5):634-7. doi: 10.1161/01.cir.103.5.634.
Results Reference
background
PubMed Identifier
9020076
Citation
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7. doi: 10.1126/science.275.5302.964.
Results Reference
background
PubMed Identifier
10202935
Citation
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999 Apr;5(4):434-8. doi: 10.1038/7434.
Results Reference
background
PubMed Identifier
10725398
Citation
Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7. doi: 10.1073/pnas.97.7.3422.
Results Reference
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Stem Cell Study for Patients With Heart Disease

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