Stem Cell Therapy in IschEmic Non-treatable Cardiac Disease

Study Overview
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Brief Summary
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The aim of the SCIENCE study is, in an international multicentre double-blind placebo-controlled study, to investigate efficacy of direct intra-myocardial injection of 100 mio. allogeneic Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASCs) in patients with reduced left ventricular Ejection Fraction (EF) (≤45%) and heart failure.

Detailed Description
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The aim of the SCIENCE study is, in an international multicentre double-blind placebo-controlled study, to investigate efficacy of direct intra-myocardial injection of 100 mio. allogeneic Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASCs) in patients with reduced left ventricular EF (≤45%) and heart failure. The primary objective is to investigate the regenerative capacity of direct intra-myocardial injection of 100 mio. allogeneic CSCC_ASCs in patients with reduced left ventricular EF (≤45%) and heart failure in a double-blind placebo-controlled design. A total of 138 patients with will be enrolled in the study and treated in a 2:1 randomization with either CSCC_ASC or placebo (saline).

Official Title
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Stem Cell Therapy in IschEmic Non-treatable Cardiac Disease - SCIENCE A European Multi-Centre Trial

Conditions
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Heart Failure

Intervention / Treatment
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* Biological: CSCC_ASC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30 to 80 years of age Signed informed consent Chronic stable ischemic heart disease Symptomatic heart failure New York Heart Association (NYHA) class II-III EF ≤ 45% on echocardiography, Computerized Tomography (CT) or Magnetic Resonances Imaging (MRI) scan Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) Maximal tolerable heart failure medication Heart failure medication unchanged two months prior to inclusion. Changes in diuretics accepted. No option for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) Patients who have had PCI or CABG within six months of inclusion must have a new coronary angiography less than one month before inclusion or at least four months after the intervention to rule out early restenosis Patients cannot be included until three months after implantation of a cardiac resynchronisation therapy device (CRTD) and until 1 month after an ICD unit Exclusion Criteria: Heart Failure (NYHA class I or IV) Acute coronary syndrome with acute reversible elevation of CKMB or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion. Constant elevated troponin due to renal failure, heart failure etc. do not exclude the patient. Other revascularisation treatment within four months of treatment If clinically indicated the patient should have a coronary angiography before inclusion Moderate to severe aortic stenosis (valve area < 1.3 cm2) or valvular disease with option for surgery or interventional therapy. Aortic valve replacement with an artificial heart valve. However, a trans-septal treatment approach can be considered in these patients. If the patient is expected to be candidate for MitraClip therapy of mitral regurgitation in the 12 months follow-up period. Diminished functional capacity for other reasons such as: obstructive pulmonary disease (COPD) with forced expiratory volume (FEV) <1 L/min, moderate to severe claudication or morbid obesity Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes > 14 109/L) or thrombocytopenia (thrombocytes < 50 109/L) Reduced kidney function (estimated Glomerular Filtration Rate (eGFR) < 30 ml/min) Left ventricular thrombus Anticoagulation treatment that cannot be paused during cell injections. Patients can continue with platelet inhibitor treatment Patients with reduced immune response or known anti-HLA (human leukocyte antigen) antibodies History with malignant disease within five years of inclusion or suspected malignity - except treated skin cancer other than melanoma Pregnant women Other experimental treatment within four weeks of baseline tests Participation in another intervention trial Life expectancy less than one year Known hypersensitivity to Dimethyl sulfoxide (DMSO), penicillin and streptomycin

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CSCC_ASC<br>Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASC) | Biological: CSCC_ASC<br>* The stem cells will be injected directly into the myocardium using the NOGA XP system (BDS, US)<br>* Other names: Cardiology Stem Cell Centre_adipose derived stem cells;|
| Placebo Comparator: Placebo<br>Saline | Biological: CSCC_ASC<br>* The stem cells will be injected directly into the myocardium using the NOGA XP system (BDS, US)<br>* Other names: Cardiology Stem Cell Centre_adipose derived stem cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| left ventricle end-systolic volume (LVESV) | The primary endpoint is change in left ventricle end-systolic volume (LVESV) from baseline to 6 months follow-up measured by ECHO, MR and CT between CSCC_ASC and placebo treated | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Serious adverse events | Incidence and severity of serious adverse events and suspected unrelated serious adverse events 12 months follow-up | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, stem cell, adipose derived stem cell, Stem cell therapy, ischemic heart disease