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

Eur Heart J. 2015 Nov 21;36(44):3061-9. doi: 10.1093/eurheartj/ehv390. Epub 2015 Sep 2.

Abstract

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 ≤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.

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.

Keywords: Dilated cardiomyopathy; Granulocyte colony-stimulating factor; Heart failure; Stem cells.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / transplantation*
  • Bone Marrow Transplantation / methods*
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiomyopathy, Dilated / therapy*
  • Combined Modality Therapy / methods
  • Exercise Tolerance / physiology
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Quality of Life
  • Stem Cell Transplantation / methods*
  • Stroke Volume / physiology
  • Treatment Outcome

Substances

  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Granulocyte Colony-Stimulating Factor