Bone Marrow Derived Adult Stem Cells for Chronic Heart Failure (REGEN-IHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Anthony Mathur, Barts & The London NHS Trust
ClinicalTrials.gov Identifier:
NCT00747708
First received: September 4, 2008
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine whether adult bone marrow derived stem/progenitor cells improve cardiac function and symptoms in patients with heart failure and to establish the optimal method of delivery of these cells.

Study hypotheses:

  • Administration of G-CSF to patients with heart failure secondary to ischaemic heart disease will lead to an increase in circulating progenitor cells as measured by peripheral CD34+ positive cell counts
  • Cardiac function and symptoms will improve in patients in whom the peripheral CD34+ counts increase in response to G-CSF administration
  • Direct coronary injection of autologous bone marrow derived stem cells will confer an additional improvement in cardiac function and symptoms above that derived from G-CSF infusion alone
  • Direct intramyocardial injection of autologous bone marrow derived stem cells will lead to an improvement in cardiac function and symptoms above that derived from G-CSF infusion alone

Condition Intervention Phase
Chronic Ischaemic Heart Failure
Drug: Granulocyte-colony stimulating factor
Procedure: Percutaneous intracoronary injection
Procedure: Percutaneous intramyocardial injection
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomised Control Trial to Compare the Effects of G-CSF and Autologous Bone Marrow Progenitor Cells Infusion on the Quality of Life and Left Ventricular Function in Patients With Heart Failure Secondary to Ischaemic Heart Disease

Resource links provided by NLM:


Further study details as provided by Barts & The London NHS Trust:

Primary Outcome Measures:
  • Change in global left ventricular ejection fraction [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Occurence of major adverse cardiac event [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Change in quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in NT-proBNP [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • change in NYHA class [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 148
Study Start Date: August 2005
Study Completion Date: May 2013
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peripheral
Patients are randomised in a 1:1 ratio to receive granulocyte-colony stimulating factor (G-CSF) or placebo injection
Drug: Granulocyte-colony stimulating factor
5 days subcutaneous injection
Other Name: G-CSF
Experimental: Percutaneous intracoronary injection
All patients will receive granulocyte-colony stimulating factor injections followed by a bone marrow aspiration. Patients will be randomised in a 1:1 ratio to receive intracoronary injections of bone marrow derived stem/progenitor cells or placebo infusion through a percutaneous route
Drug: Granulocyte-colony stimulating factor
5 days subcutaneous injection
Other Name: G-CSF
Procedure: Percutaneous intracoronary injection
Bone marrow derived stem/progenitor cells or placebo infusion is delivered through an over-the-wire balloon catheter into the target coronary vessels using a stop-flow technique.
Experimental: Percutaneous intramyocardial injection
All patients will receive granulocyte-colony stimulating factor injections followed by a bone marrow aspiration. Patients will be randomised in a 1:1 ratio to receive intramyocardial injections of bone marrow derived stem/progenitor cells or placebo infusion through a percutaneous route
Drug: Granulocyte-colony stimulating factor
5 days subcutaneous injection
Other Name: G-CSF
Procedure: Percutaneous intramyocardial injection
Direct intramyocardial injections of bone marrow derived stem/progenitor cells or placebo will be delivered using the electromechanical NOGA mapping and injection system

Detailed Description:

The study involves three arms that compare the method of autologous bone marrow cel administration in patients with chronic heart failure. Each arm has a comparative group that contains either saline injection (peripheral arm that injects GCSF alone) or serum (the two interventional arms-intracoronary and intramyocardial injection).

The protocol (on the advice of the ethics committee) is divided into a 58 patients pilot study followed by recruitment into the intramyocardial arm (30 patients randomised 1:1 cells in serum vs serum alone) and then recruitment into the intracoronary and peripheral arms (30 patients randomised 1:1 cells in serum vs serum alone in each arm).

The study has been powered around the use of advanced imaging to measure within group changes in ejection fraction at 12 months as the primary end point.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptomatic patients with a diagnosis of heart failure secondary to ischaemic heart disease who are on optimal heart failure treatment and no further treatment options available
  • Patient has been considered for an implantable defibrillator in keeping with NICE guidelines

Exclusion Criteria:

  • Recent acute coronary syndrome as judged by a rise of Troponin above normal values in the last 6 months
  • 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 secondary to a reversible cause 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
  • Contra-indication for bone marrow aspiration
  • Known active infection
  • Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) syphilis or HTLV
  • Lifestyle with high risk for infection with HIV, HBV or HCV syphilis or HTLV
  • Serum creatinine >200 umol/L
  • Chronic inflammatory disease
  • Serious known concomitant disease with a life expectancy of less than one year
  • Follow-up impossible (no fixed abode, etc)
  • Previous participation in this study
  • Female subjects of childbearing potential
  • Atrial fibrillation
  • Patients who have responded to the implantation of a biventricular pacemaker
  • Weight >140kg
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747708

Locations
United Kingdom
London Chest Hospital, Barts and the London NHS Trust
London, United Kingdom, E2 9JX
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
Principal Investigator: Anthony Mathur, FRCP FESC Ph Barts and the London NHS Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Anthony Mathur, Lead Cardiologist, Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT00747708     History of Changes
Other Study ID Numbers: 04/Q0603/13, 2005-002706-27 (EudraCT)
Study First Received: September 4, 2008
Last Updated: October 8, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Barts & The London NHS Trust:
heart failure
coronary heart disease
adult stem cells
bone marrow progenitor cells
bone marrow stem cells
autologous
granulocyte-colony stimulating factor
left ventricular function
intracoronary injection
intramyocardial injection

Additional relevant MeSH terms:
Myocardial Ischemia
Heart Diseases
Heart Failure
Ischemia
Cardiovascular Diseases
Vascular Diseases
Pathologic Processes
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014