Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
Peripheral	granulocyte colony stimulating factor (GCSF)	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
Interventional arm	bone marrow mononuclear cells	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

Primary Outcome Measures

Name	Time	Method
Change in left ventricular ejection fraction as measured by cardiac magnetic resonance imaging or computerised tomography	3 months

Secondary Outcome Measures

Name	Time	Method
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
The occurrence of major arrhythmias defined by symptomatic ventricular tachycardia or survived sudden death	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

Recruitment & Eligibility