DEtection of Cellular Inflammation With FERumoxytol in the HEART

Study Overview
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Brief Summary
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To non-invasively image myocardial accumulation of ultrasmall superparamagnetic particles of iron oxide (USPIOs) by an increase in R2* values (compared to controls) within the myocardium of patients with: i. cardiac transplantation ii. acute myocarditis iii. suspected cardiac sarcoidosis

Detailed Description
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Ferumoxytol is a 'smart' magnetic resonance contrast agent consisting of ultrasmall superparamagnetic particles of iron oxide (USPIOs) that are taken up by macrophages. Concentration of USPIOs within macrophages changes the tissue relaxation properties and this can be detected by magnetic resonance imaging using R2* maps. In a recent early proof-of-concept study, we demonstrated that macrophages could be detected with USPIOs in the penumbra and infarct zone of the myocardium in patients with a recent myocardial infarction. The investigators therefore wish to establish whether USPIOs can be used to identify cellular inflammation within the myocardium in three distinct clinical conditions that currently lack a non-invasive diagnostic imaging test: cardiac allograft rejection, viral myocarditis and cardiac sarcoidosis. If successful, this would not only provide a useful diagnostic test but would also be a method of monitoring disease progression or response to therapy.

Official Title
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DEtection of Cellular Inflammation With FERumoxytol in the HEART

Conditions
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Cardiac Transplant, Cardiac Sarcoid, Myocarditis, Healthy Volunteers

Intervention / Treatment
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* Drug: Ferumoxytol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the four conditions below: Patients having undergone cardiac transplant Patients diagnosed clinically with myocarditis of any aetiology (eg viral, septic, post chemotherapeutic etc) Patients clinically diagnosed with cardiac sarcoidosis Healthy volunteers Age > 18 years. Exclusion Criteria: Contraindication to magnetic resonance imaging scanning identified from magnetic resonance imaging safety questionnaire Patients refusing or unable to give informed consent Renal failure (estimated glomerular filtration rate <30 mL/min) Polycythemia Contraindication to ferumoxytol (previous allergic drug reaction, any immune or inflammatory conditions (eg, systemic lupus erythematosus, rheumatoid arthritis, history of severe asthma, eczema or other atopic allergy)), evidence of known iron overload, hemochromatosis, known hypersensitivity to ferumoxytol or its components or anaemia not caused by iron deficiency. Known allergy to dextran- or iron-containing compounds. Diagnosis of myocardial infarction within 1 month. Pregnancy or Breast-feeding. Women of child bearing age not ensuring reliable methods of contraception. Female participants of child bearing age will be asked if they are ensuring reliable methods of contraception prior to each administration of USPIO and MRI scan. If use of reliable contraception cannot be confirmed, the participant will be withdrawn.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Myocarditis<br> | Drug: Ferumoxytol<br>* Infusion following between paired MRI scans<br>|
| Active Comparator: Cardiac sarcoid<br> | Drug: Ferumoxytol<br>* Infusion following between paired MRI scans<br>|
| Active Comparator: Cardiac Transplant<br> | Drug: Ferumoxytol<br>* Infusion following between paired MRI scans<br>|
| Placebo Comparator: Healthy Volunteers<br> | Drug: Ferumoxytol<br>* Infusion following between paired MRI scans<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Myocardial Cellular Inflammation. | Assessment of Myocardial Cellular Inflammation through the increase in R2* value on post USPIO imaging versus baseline imaging. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of R2* values with circulating inflammatory markers | Comparison of circulating inflammatory markers in peripheral blood with myocardial inflammation (seen on cardiac R2* maps) . | 1 year | 
| Does clinical condition correlate with inflammation seen on R2* maps. (assessed by reduction in R2* values) | Does treatment or recovery from these inflammatory myocardial conditions reduce or halt uptake of USPIOs as assessed by reduction in R2* values. | 1 year | 
| Do higher R2* correlate with poorer outcome? (assessed by deterioration in ejection fraction or increase in late gadolinium enhancement) | Do patients with higher R2* values have worse outcomes assessed by deterioration in ejection fraction or increase in late gadolinium enhancement. | 1 year |