Inflammatory Cell Trafficking After Myocardial Infarction

NCT01127113 | Withdrawn

• 1 other identifier: EDO001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Infarction; Inflammation

Keywords

Myocardial infarction; Magnetic resonance imaging; Nanoparticles; Mononuclear cells; Cell tracking

Outcome Measures

Primary Outcomes (1)

• Change in cardiac MRI signal intensity from baseline after administration of labelled vs. unlabelled mononuclear cells.

  90 days

Secondary Outcomes (1)

• Correlation of myocardial MRI signal intensity change from baseline with markers of systemic inflammation.

  90 days

Study Arms (3)

SPIO-labelled mononuclear cells

ACTIVE COMPARATOR

Other: Infusion of investigational product; Other: Cardiac magnetic resonance imaging

Unlabelled mononuclear cells

PLACEBO COMPARATOR

Other: Infusion of investigational product; Other: Cardiac magnetic resonance imaging

SPIO alone

ACTIVE COMPARATOR

Other: Infusion of investigational product; Other: Cardiac magnetic resonance imaging

Interventions

Infusion of investigational product OTHER

The investigational product will be delivered via intravenous infusion

Also known as: The investigational product will be either:, 1) Unlabelled autologous mononuclear cells, 2) Endorem (Guerbet, Paris) contrast alone, 3) Autologous mononuclear cells labelled with Endorem

SPIO alone; SPIO-labelled mononuclear cells; Unlabelled mononuclear cells

Cardiac magnetic resonance imaging OTHER

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

SPIO alone; SPIO-labelled mononuclear cells; Unlabelled mononuclear cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presentation with acute ST segment elevation myocardial infarction:
• mm ST elevation in at least two contiguous limb leads, or
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Edinburgh: lead
• British Heart Foundation: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Midlothian, EH16 4SU, United Kingdom

Location

MeSH Terms

Conditions

Myocardial Infarction; Inflammation

Interventions

ferumoxides; Contrast Media

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• David E Newby, MD, PhD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: May 20, 2010
• Study Start: January 1, 2010
• Primary Completion: November 1, 2015
• Study Completion: March 1, 2016
• Last Updated: May 2, 2024

Record last verified: 2014-12

Locations

GB (1)