Inflammatory Cell Trafficking After Myocardial Infarction

Sponsor

University of Edinburgh (Other)

Overall Status

Suspended

CT.gov ID

NCT01127113

Collaborator

British Heart Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Myocardial infarction (heart attack) is usually the consequence of rupture of a fatty 'plaque' in a heart artery. The presence of this fat and debris causes the propagation of a blood clot and blockage of the artery. The heart muscle normally supplied by the artery becomes deprived of oxygen and, if starved for long enough, this area of muscle dies. Much of the heart muscle damage is caused by overactivation of inflammatory cells. Whilst inflammation can be beneficial in healing processes, there is accumulating evidence that overactivation of inflammatory processes contributes to further muscle damage and cell death during myocardial infarction. We have recently developed a means of labelling human blood cells with 'nanoparticles' of iron oxide which can then safely be reinjected into the blood to allow the cells to be tracked and seen in the body using a conventional magnetic resonance scanner.

In the proposed study we aim to recruit patients with recent heart attacks to perform similar cell labelling and reinjection of labelled cells into the same volunteer's blood stream via the arm to track the fate of the blood cells over the course of days to months. We think that the labelled inflammatory cells will 'home' to the site of the heart attack and will be visible using magnetic resonance imaging (MRI) of the heart. We aim not only to highlight the role of inflammatory cells in myocardial infarction, but also propose that, if successful, this technique could be used in the future to assess the effects of antiinflammatory treatments currently being developed for the treatment of patients with heart attacks. The technique could also be extended to allow labelling of other cell types, including stem cells, to let us further understand how these cells may contribute to repair of damaged organs including the heart.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction Inflammation	Other: Infusion of investigational product Other: Cardiac magnetic resonance imaging	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

66 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Inflammatory Cell Labelling and Tracking With Magnetic Resonance Imaging After Myocardial Infarction

Study Start Date :

Jan 1, 2010

Anticipated Primary Completion Date :

Nov 1, 2015

Anticipated Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SPIO-labelled mononuclear cells	Other: Infusion of investigational product The investigational product will be delivered via intravenous infusion Other Names: The investigational product will be either: 1) Unlabelled autologous mononuclear cells 2) Endorem (Guerbet, Paris) contrast alone 3) Autologous mononuclear cells labelled with Endorem Other: Cardiac magnetic resonance imaging Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.
Placebo Comparator: Unlabelled mononuclear cells	Other: Infusion of investigational product The investigational product will be delivered via intravenous infusion Other Names: The investigational product will be either: 1) Unlabelled autologous mononuclear cells 2) Endorem (Guerbet, Paris) contrast alone 3) Autologous mononuclear cells labelled with Endorem Other: Cardiac magnetic resonance imaging Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.
Active Comparator: SPIO alone	Other: Infusion of investigational product The investigational product will be delivered via intravenous infusion Other Names: The investigational product will be either: 1) Unlabelled autologous mononuclear cells 2) Endorem (Guerbet, Paris) contrast alone 3) Autologous mononuclear cells labelled with Endorem Other: Cardiac magnetic resonance imaging Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.

Arm

Intervention/Treatment

Active Comparator: SPIO-labelled mononuclear cells

Other: Infusion of investigational product

The investigational product will be delivered via intravenous infusion

Other Names:

The investigational product will be either:

1) Unlabelled autologous mononuclear cells

2) Endorem (Guerbet, Paris) contrast alone

3) Autologous mononuclear cells labelled with Endorem

Other: Cardiac magnetic resonance imaging

Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.

Placebo Comparator: Unlabelled mononuclear cells

Other: Infusion of investigational product

The investigational product will be delivered via intravenous infusion

Other Names:

The investigational product will be either:

1) Unlabelled autologous mononuclear cells

2) Endorem (Guerbet, Paris) contrast alone

3) Autologous mononuclear cells labelled with Endorem

Other: Cardiac magnetic resonance imaging

Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.

Active Comparator: SPIO alone

Other: Infusion of investigational product

The investigational product will be delivered via intravenous infusion

Other Names:

The investigational product will be either:

1) Unlabelled autologous mononuclear cells

2) Endorem (Guerbet, Paris) contrast alone

3) Autologous mononuclear cells labelled with Endorem

Other: Cardiac magnetic resonance imaging

Cardiac MRI will be performed prior to infusion of investigational product and 1, 2, 7 and 30 days after.

Outcome Measures

Primary Outcome Measures

Change in cardiac MRI signal intensity from baseline after administration of labelled vs. unlabelled mononuclear cells. [90 days]

Secondary Outcome Measures

Correlation of myocardial MRI signal intensity change from baseline with markers of systemic inflammation. [90 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Presentation with acute ST segment elevation myocardial infarction:
1 mm ST elevation in at least two contiguous limb leads, or
2 mm ST elevation in at least two contiguous praecordial leads, or new onset bundle branch block
Successful treatment with primary percutaneous coronary intervention Restoration of TIMI grade 3 flow in infarct-related artery
Troponin I ≥10 IU/mL at 12 hours after the onset of chest pain
Age 18 - 80 years

Exclusion Criteria:

Left main stem or severe multi-vessel coronary artery disease
Continued symptoms of angina at rest or minimal exertion
Atrial fibrillation
Symptomatic heart failure; Killip Class ≥2.
Hepatic or renal failure (estimated glomerular filtration rate <25 mL/min)
Terminal illness or malignancy
Anaemia
Contraindication to magnetic resonance imaging
Hepatitis B, hepatitis C, HTLV, HIV or syphilis infection
Patients at risk of allergy to protamine (fish allergy, infertile men, previous vasectomy)