Bone Marrow Derived Adult Stem Cells for Chronic Heart Failure

NCT00747708 | Completed Phase 2 DMC

• 2 other identifiers: 04/Q0603/132005-002706-27 (EudraCT)
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Ischaemic Heart Failure

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in global left ventricular ejection fraction

  12 months

Secondary Outcomes (5)

• Change in quality of life

  6 months

• Occurence of major adverse cardiac event

  12 months

• Change in quality of life

  12 months

• Change in NT-proBNP

  6 months

• change in NYHA class

  12 months

Study Arms (3)

Peripheral

EXPERIMENTAL

Patients are randomised in a 1:1 ratio to receive granulocyte-colony stimulating factor (G-CSF) or placebo injection

Drug: Granulocyte-colony stimulating factor

Percutaneous intracoronary injection

EXPERIMENTAL

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; Procedure: Percutaneous intracoronary injection

Percutaneous intramyocardial injection

EXPERIMENTAL

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; Procedure: Percutaneous intramyocardial injection

Interventions

Granulocyte-colony stimulating factor DRUG

5 days subcutaneous injection

Also known as: G-CSF

Percutaneous intracoronary injection; Percutaneous intramyocardial injection; Peripheral

Percutaneous intracoronary injection PROCEDURE

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.

Percutaneous intracoronary injection

Percutaneous intramyocardial injection PROCEDURE

Direct intramyocardial injections of bone marrow derived stem/progenitor cells or placebo will be delivered using the electromechanical NOGA mapping and injection system

Percutaneous intramyocardial injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

London Chest Hospital, Barts and the London NHS Trust

London, London, E2 9JX, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure; Coronary Disease

Interventions

Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Anthony Mathur, FRCP FESC Ph

  Barts and the London NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lead Cardiologist

Study Record Dates

• First Submitted: September 4, 2008
• First Posted: September 5, 2008
• Study Start: August 1, 2005
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2013
• Last Updated: October 9, 2013

Record last verified: 2013-10

Locations

GB (1)