Allogeneic Stem Cell Therapy in Heart Failure

Study Overview
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Brief Summary
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The present aim is to perform at clinical double-blind placebo-controlled Cardiology Stem Cell Centre - Adipose Stem Cells (CSCC_ASC) study in heart failure patients to investigate the regenerative capacity of the CSCC_ASC treatment.

Detailed Description
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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 Ejection Fraction (EF) (≤45%) and heart failure in a double-blind placebo-controlled design. A total of 81 patients with will be enrolled in the study and treated in a 2:1 randomization with either CSCC_ASC or placebo (saline). The primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months follow-up.

Official Title
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Allogeneic Adipose Tissue-derived Stromal/Stem Cell Therapy in Patients With Ischemic Heart Disease and Heart Failure: A Phase II Danish Multicentre Study

Conditions
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Heart Failure

Intervention / Treatment
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* Biological: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC)
* Biological: Placebo


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% Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) in sinus rhythm and plasma NT-pro-BNP > 422 pg/ml (> 450 pmol/L) in patients with atrial fibrillation Maximal tolerable heart failure medication Medication unchanged two months prior to inclusion 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 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 Exclusion Criteria: Heart Failure (NYHA I or IV) Acute coronary syndrome with elevation of creatine kinase (CK) isoenzyme MB (CKMB) or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion 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 mm2) or valvular disease with option for surgery. 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) Anticoagulation treatment that cannot be paused during cell injections Patients with reduced immune response 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

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC)<br>Allogeneic adipose derived stromal cells | Biological: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC)<br>* Direct intramyocardial injection of CSCC_ASC<br>|
| Placebo Comparator: Placebo<br>Saline | Biological: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in left ventricle end-systolic volume (LVESV) from base line to 6 months follow-up measured by echocardiography and computerized tomography | change in left ventricle end-systolic volume (LVESV) from base line to 6 months follow-up measured by echocardiography and computerized tomography | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Safety is evaluated by the incidence and severity of serious adverse events and suspected unrelated serious adverse events at 12 months follow-up | 12 months | 
| Efficacy left ventricle | change in left ventricle ejection fraction (EF) measured by echocardiography and computerized tomography | 6 months | 
| Efficacy clinical function assessed by change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6 months follow-up | change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6 months follow-up | 6 months | 
| Efficacy clinical function assessed by change in Seattle Angina Questionnaire and 6 min walking test from baseline to 6 months follow-up | change in Seattle Angina Questionnaire and 6 min walking test from baseline to 6 months follow-up | 6 months | 
| Efficacy clinical function assessed by change in 6 min walking test from baseline to 6 months follow-up | change in 6 min walking test from baseline to 6 months follow-up | 6 months | 
| Efficacy clinical function assessed by change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 12 months follow-up | change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 12 months follow-up | 12 months | 
| Efficacy clinical function assessed by change in Seattle Angina Questionnaire and 6 min walking test from baseline to 12 months follow-up | change in Seattle Angina Questionnaire and 6 min walking test from baseline to 12 months follow-up | 12 months | 
| Efficacy clinical function assessed by change in 6 min walking test from baseline to 12 months follow-up | change in 6 min walking test from baseline to 12 months follow-up | 12 months |