Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy (REGENERATE-DCM)

• Change in: Concentrations of NT-proBNP (cardiac enzyme) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Changes in V02 max (exercise capacity) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Changes in ejection fraction, ventricular dimensions as measured by cardiac MRI/ CT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Functional class changes according to NYHA and quality of life (QoL - EQ-5D & Kansas City) questionnaires [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• 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) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
• Hospitalization for Heart failure & the occurrence of major arrhythmias defined as symptomatic ventricular tachycardia or survived sudden death [ Time Frame: 3 months ] [ Designated as safety issue: No ]

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

• Drug: granulocyte colony stimulating factor (GCSF)
  10mcg/kg per day 5 days
  Other Name: Lenograstim, Granocyte™, Chugai Pharma UK, Limited
• Procedure: bone marrow mononuclear cells
  intra coronary injection of stem cells or placebo

• Experimental: Peripheral
  Half the patients will be randomised to the non-interventional part of the trial. In this subgroup of patients, half will be randomised to placebo injection and half to receive a 5 day course of G-CSF(Granocyte™) injection
  Intervention: Drug: granulocyte colony stimulating factor (GCSF)
• Experimental: Interventional arm
  All patients randomised to the interventional arm of the study will receive a 5 day course of G-CSF (Granocyte™) by subcutaneous injection followed by bone marrow aspiration. Patients will then receive either stem cells or placebo via intracoronary injection
  Intervention: Procedure: bone marrow mononuclear cells

Inclusion Criteria:

• Symptomatic patients with a confirmed diagnosis of dilated cardiomyopathy (NYHA II-III) attending the '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
• Documented latest ejection fraction >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 (ejection fraction <10%) prior to randomisation
• Congenital cardiac disease
• Cardiomyopathy 2o 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 (see section 7.7)

• Royal Brompton & Harefield NHS Foundation Trust
• University College London Hospitals