Bone Marrow Derived Adult Stem Cells for Chronic Heart Failure

NCT ID: NCT00747708

Last Updated: 2013-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Study Completion Date

2013-05-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Chronic Ischaemic Heart Failure

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Peripheral

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

Group Type EXPERIMENTAL

Granulocyte-colony stimulating factor

Intervention Type DRUG

5 days subcutaneous injection

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

Group Type EXPERIMENTAL

Granulocyte-colony stimulating factor

Intervention Type DRUG

5 days subcutaneous injection

Percutaneous intracoronary injection

Intervention Type 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 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

Group Type EXPERIMENTAL

Granulocyte-colony stimulating factor

Intervention Type DRUG

5 days subcutaneous injection

Percutaneous intramyocardial injection

Intervention Type PROCEDURE

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

Interventions

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Granulocyte-colony stimulating factor

5 days subcutaneous injection

Intervention Type DRUG

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.

Intervention Type 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

Intervention Type PROCEDURE

Other Intervention Names

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G-CSF

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Barts & The London NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Anthony Mathur

Lead Cardiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anthony Mathur, FRCP FESC Ph

Role: PRINCIPAL_INVESTIGATOR

Barts and the London NHS Trust

Locations

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London Chest Hospital, Barts and the London NHS Trust

London, London, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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2005-002706-27 (EudraCT)

Identifier Type: -

Identifier Source: secondary_id

04/Q0603/13

Identifier Type: -

Identifier Source: org_study_id