PMID- 26333366 OWN - NLM STAT- MEDLINE DCOM- 20160913 LR - 20220316 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 36 IP - 44 DP - 2015 Nov 21 TI - 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. PG - 3061-9 LID - 10.1093/eurheartj/ehv390 [doi] AB - AIMS: 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. METHODS AND RESULTS: Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of /=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. CONCLUSION: 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. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Hamshere, Stephen AU - Hamshere S AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Arnous, Samer AU - Arnous S AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Choudhury, Tawfiq AU - Choudhury T AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Choudry, Fizzah AU - Choudry F AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Mozid, Abdul AU - Mozid A AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Yeo, Chia AU - Yeo C AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Barrett, Catherine AU - Barrett C AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Saunders, Natalie AU - Saunders N AD - Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK. FAU - Gulati, Ankur AU - Gulati A AD - Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Imperial College London, Sydney Street, London UK SW3 6NP, UK. FAU - Knight, Charles AU - Knight C AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Locca, Didier AU - Locca D AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Davies, Ceri AU - Davies C AD - 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. FAU - Cowie, Martin R AU - Cowie MR AD - Imperial College London (Royal Brompton Hospital), London UK SW3 6NP, UK. FAU - Prasad, Sanjay AU - Prasad S AD - Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Imperial College London, Sydney Street, London UK SW3 6NP, UK. FAU - Parmar, Mahesh AU - Parmar M AD - Cancer Division, Medical Research Council, Clinical Trials Unit, London, UK. FAU - Agrawal, Samir AU - Agrawal S AD - Stem Cell Laboratory, Barts Health NHS Trust and Blizard Institute, Queen Mary University of London, London, UK. FAU - Jones, Daniel AU - Jones D AD - Department of Cardiology, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK. FAU - Martin, John AU - Martin J AD - British Heart Foundation Laboratories, Department of Medicine, University College London, London WC1E 6JJ, UK. FAU - McKenna, William AU - McKenna W AD - Institute of Cardiovascular Science, University College London, The Heart Hospital, UCLH, 16-18 Westmoreland Street, London W1G 8PH, UK. FAU - Mathur, Anthony AU - Mathur A AD - 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. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150902 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM CIN - Eur Heart J. 2015 Nov 21;36(44):3070-3. PMID: 26419622 MH - Adult Stem Cells/*transplantation MH - Bone Marrow Transplantation/*methods MH - Cardiomyopathy, Dilated/physiopathology/*therapy MH - Combined Modality Therapy/methods MH - Exercise Tolerance/physiology MH - Female MH - Granulocyte Colony-Stimulating Factor/*therapeutic use MH - Humans MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/metabolism MH - Peptide Fragments/metabolism MH - Quality of Life MH - Stem Cell Transplantation/*methods MH - Stroke Volume/physiology MH - Treatment Outcome PMC - PMC4654774 OTO - NOTNLM OT - Dilated cardiomyopathy OT - Granulocyte colony-stimulating factor OT - Heart failure OT - Stem cells EDAT- 2015/09/04 06:00 MHDA- 2016/09/14 06:00 PMCR- 2015/09/02 CRDT- 2015/09/04 06:00 PHST- 2015/04/19 00:00 [received] PHST- 2015/07/24 00:00 [accepted] PHST- 2015/09/04 06:00 [entrez] PHST- 2015/09/04 06:00 [pubmed] PHST- 2016/09/14 06:00 [medline] PHST- 2015/09/02 00:00 [pmc-release] AID - ehv390 [pii] AID - 10.1093/eurheartj/ehv390 [doi] PST - ppublish SO - Eur Heart J. 2015 Nov 21;36(44):3061-9. doi: 10.1093/eurheartj/ehv390. Epub 2015 Sep 2.