Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy

Study Overview
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Brief Summary
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A randomised, double-blind, placebo-controlled trial to evaluate the role of intracoronary injection of progenitor cells compared to placebo injection in patients with Dilated Cardiomyopathy who have been pre-treated with G-CSF (Granocyte™) injections for 5 days, and patients treated with a 5 day course of G-CSF (Granocyte™) injection only compared to placebo injection

Official Title
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Randomised Controlled Trial to Compare the Effects of G-CSF (Granocyte™) and Autologous Bone Marrow Progenitor Cells on Quality of Life and Left Ventricular Function in Patients With Idiopathic Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: granulocyte colony stimulating factor (GCSF)
* Procedure: bone marrow mononuclear cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic patients with a confirmed diagnosis of dilated cardiomyopathy (NYHA II-III) attending their local 'Heart Failure clinic' who are on optimal heart failure treatment, under supervision from their physician or heart failure nurse specialist, and have no other treatment options Patients who are NYHA II that have been hospitalised with a dilated cardiomyopathy related condition Coronary angiography will be performed where necessary to confirm the diagnosis and ensure no other conventional treatment options are indicated Prior to recruitment to the study patients at risk of ventricular arrhythmia will have undergone electrophysiological assessment and appropriate clinical management (including implantable defibrillator insertion) where indicated (as per NICE guidelines) Exclusion Criteria: NYHA I Referral hospitals most recent documented ejection fraction of >45% (any imaging modality) The presence of cardiogenic shock The presence of acute left and/or right sided pump failure as judged by the presence of pulmonary oedema and/or new peripheral oedema Known severe pre-existent left ventricular dysfunction (with a documented ejection fraction of <10% from referral hospital) prior to randomisation Congenital cardiac disease Cardiomyopathy secondary to a reversible cause that has not been treated e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity & chronic uncontrolled tachycardia Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy Previous cardiac surgery Contra-indication for bone marrow aspiration Known active infection Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), HTLV or syphilis. Chronic inflammatory disease requiring ongoing medication Serious known concomitant disease with a life expectancy of less than one year Follow-up impossible (no fixed abode, etc) Patients with an irregular heart rhythm (AF allowed if paced in a regular rhythm) Patients with renal impairment (Creatinine >200mmol/L) Neoplastic disease without documented remission within the past 5 years Weight>140kg Subjects of childbearing potential

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Peripheral<br>Half the patients will be randomised to the non-interventional part of the trial. In this subgroup of patients will be randomised 1:1 to 5 day course of subcutaneous placebo injections or a 5 day course of G-CSF(Granocyte™) subcutaneous injections | Drug: granulocyte colony stimulating factor (GCSF)<br>* 10mcg/kg per day 5 days<br>* Other names: Lenograstim, Granocyte™, Chugai Pharma UK, Limited;|
| Experimental: Interventional arm<br>In the subgroup of the interventional arm patients will be randomised 1:1 to receive a 5 day course of subcutaneous G-CSF (Granocyte™) injections and bone marrow aspiration at day 5, they will then receive either stem cells or placebo via intracoronary injection | Procedure: bone marrow mononuclear cells<br>* intra coronary injection of stem cells or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction as measured by cardiac magnetic resonance imaging or computerised tomography |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in: Concentrations of N-terminal prohormone of brain natriuretic peptide (cardiac enzyme) |  | 3 months and 12 months | 
| Changes in V02 max (exercise capacity) |  | 3 months and 12 months | 
| Changes in left ventricular ejection fraction, ventricular dimensions as measured by cardiac magnetic resonance imaging or computerised tomography |  | 3 months and 12 months | 
| Functional class changes according to NYHA and quality of life (QoL - EQ-5D & Kansas City) questionnaires |  | 3 months and 12 months | 
| Occurrence of a Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction (CK / CK-MB over 2 times the upper limit of normal) |  | 3 months and 12 months | 
| Hospitalization for Heart failure & the occurrence of major arrhythmias defined as symptomatic ventricular tachycardia or survived sudden death |  | 3 months and 12 months | 
| The occurrence of major arrhythmias defined by symptomatic ventricular tachycardia or survived sudden death |  | 3 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dilated cardiomyopathy, adult stem cells, bone marrow progenitor cells, bone marrow stem cells, autologous, granulocyte-colony stimulating factor, intracoronary injection, left ventricular function, To determine if patient's own bone marrow derived stem cells can be used to improve cardiac function