In Vivo Tracking of USPIO Labeled MSC in the Heart

Study Overview
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Brief Summary
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To evaluate the ability to trace iron oxide-labeled mesenchymal stromal cells with magnetic resonance imaging (MRI) after NOGA-guided injection therapy into the myocardium in patients with ischemic heart disease.

Detailed Description
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Aims: To evaluate the ability to trace iron oxide-labeled mesenchymal stromal cells with magnetic resonance imaging (MRI) after NOGA-guided injection therapy into the myocardium. To evaluate the safety and efficacy of treatment with iron oxide-labeled mesenchymal stromal cells to form new heart muscle cells and blood vessels in the myocardium submitted by NOGA-guided injection therapy in the myocardium in order to improve myocardial blood flow and reduce patients' symptoms. Patient Population: Patients with coronary artery disease not treatable with additional bypass surgery or percutaneous coronary intervention who have angina pectoris (Canadian Cardiovascular Society (CCS) class II-III) or angina equivalent shortness of breath (New York Heart Association (NYHA) class II -III). Study Design A prospective, non-randomized, pilot study including 5-10 patients. Patients will by means of the percutaneous NOGA injection catheter system receive 12-15 intramyocardial injections. The number depending on the amount of cultured cells and distributed uniformly in the peripheral zone of a presumed ischemic area in the left ventricle demonstrated by angiography, magnetic resonance imaging and NOGA mapping.

Official Title
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In Vivo MRI Tracking of Mesenchymal Stromal Cells Labeled With Ultra-Small Paramagnetic Iron Oxide Particles After Intramyocardial Transplantation in Patients With Chronic Ischemic Heart Disease

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Combination Product: USPIO labeled MSC injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 30 and 80 years. Signed informed consent. Chronic stable ischemic heart disease New York Heart Association (NYHA) class II-IV or Canadian Cardiovascular Society (CCS) class II-IV Maximal tolerable angina and/or heart failure medication. Angiography within 12 months of inclusion. Angiography must have at least one larger coronary vessel with a significant stenosis with no option for revascularization (Angiographies evaluated by an independent thoracic surgeon and an interventional cardiologist). Patients who have had revascularization done within 6 months of inclusion must have a new angiography at least 4 months after the intervention to rule out early restenosis. Exclusion Criteria: Pregnant or fertile women. Clinical significant anemia, leukopenia, leukocytosis or thrombocythemia. Diminished functional capacity for other reasons such as: chronic obstructive pulmonary disease (COLD) with Forced Expiratory Volume in 1 second (FEV1)<1 L/min, moderate to severe claudication or morbid obesity. Patients with reduced immune response or treated with immunosuppressive medication. Moderate to severe valvular disease or valvular disease with option for valvular surgery. Acute coronary syndrome with elevation of coronary markers, stroke or Transitory Cerebral Ischemia (TCI) within 6 weeks of inclusion. History with malignant disease within 5 years of inclusion or suspected malignity. Other experimental treatment within 4 weeks of baseline evaluation. Other revascularization treatment within 4 months of treatment. Contraindications for Magnetic Resonance Imaging (MRI) such as: Claustrophobia, pacemaker, Implantable Cardioverter Defibrillator (ICD) unit, metal fragments or metal implants in the cranium

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: USPIO labeled MSC injection<br>USPIO labeled MSC injection | Combination Product: USPIO labeled MSC injection<br>* USPIO labeled MSC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSC identification using MRI in-vivo on day 0 | Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 0 after injection into the myocardium by MRI. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSC identification using MRI in-vivo on day 1 | Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 1 | 1 day | 
| MSC identification using MRI in-vivo on day 7 | Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 7 | 7 days | 
| MSC identification using MRI in-vivo after 2 weeks | Being able to identify the iron-oxide labeled mesenchymal stromal cells after 2 weeks | 2 weeks | 
| MSC identification using MRI in-vivo after 4 weeks | Being able to identify the iron-oxide labeled mesenchymal stromal cells after 4 weeks | 4 weeks | 
| MSC identification using MRI in-vivo after 8 weeks | Being able to identify the iron-oxide labeled mesenchymal stromal cells after 8 weeks | 8 weeks | 
| MSC identification using MRI in-vivo after 12 weeks | Being able to identify the iron-oxide labeled mesenchymal stromal cells after 12 weeks | 12 weeks | 
| MSC identification using MRI in-vivo after 26 weeks | Being able to identify the iron-oxide labeled mesenchymal stromal cells after 26 weeks | 26 weeks | 
| Cardiac pump function changes | Left ventricular ejection fraction, systolic and diastolic volumes after 12 weeks | 12 weeks | 
| Cardiac pump function changes | Left ventricular ejection fraction, systolic and diastolic volumes after 26 weeks | 26 weeks | 
| CCS class | Canadian Cardiovascular Society (CCS) class after 12 weeks | 12 weeks | 
| CCS class | Canadian Cardiovascular Society (CCS) class after 26 weeks | 26 weeks | 
| Seattle Angina Questionnaire | Seattle Angina Questionnaire after 12 weeks | 12 weeks | 
| Seattle Angina Questionnaire | Seattle Angina Questionnaire after 26 weeks | 26 weeks | 
| Weekly number of angina attacks | Weekly number of angina attacks after 12 weeks | 12 weeks | 
| Weekly number of angina attacks | Weekly number of angina attacks after 26 weeks | 26 weeks | 
| Weekly nitroglycerin consumption | Weekly nitroglycerin consumption after 12 weeks | 12 weeks | 
| Weekly nitroglycerin consumption | Weekly nitroglycerin consumption after 26 weeks | 26 weeks | 
| Adverse events | Adverse events registration | 6 months |