Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial.
OBJECTIVE
The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction.


RESULTS
Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups.


CONCLUSIONS
This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Stephen
S
Hamshere
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Samer
S
Arnous
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Tawfiq
T
Choudhury
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Fizzah
F
Choudry
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Abdul
A
Mozid
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Chia
C
Yeo
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Catherine
C
Barrett
Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK.
Natalie
N
Saunders
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Imperial College London, Sydney Street, London UK SW3 6NP, UK.
Ankur
A
Gulati
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Charles
C
Knight
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Didier
D
Locca
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK Barts Health NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital, Barts Health NHS Trust, London E2 9JX, UK.
Ceri
C
Davies
Imperial College London (Royal Brompton Hospital), London UK SW3 6NP, UK.
Martin R
MR
Cowie
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Imperial College London, Sydney Street, London UK SW3 6NP, UK.
Sanjay
S
Prasad
Cancer Division, Medical Research Council, Clinical Trials Unit, London, UK.
Mahesh
M
Parmar
Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK.
Samir
S
Agrawal
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK.
Daniel
D
Jones
British Heart Foundation Laboratories, Department of Medicine, University College London, London WC1E 6JJ, UK.
John
J
Martin
Institute of Cardiovascular Science, University College London, The Heart Hospital, UCLH, 16-18 Westmoreland Street, London W1G 8PH, UK.
William
W
McKenna
Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK Barts Health NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital, Barts Health NHS Trust, London E2 9JX, UK a.mathur@qmul.ac.uk.
Anthony
A
Mathur
D053687:Adult Stem Cells / Q000637:transplantation*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011788:Quality of Life; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D016179:Granulocyte Colony-Stimulating Factor
Dilated cardiomyopathy; Granulocyte colony-stimulating factor; Heart failure; Stem cells