DEtection of Cellular Inflammation With FERumoxytol in the HEART

Phase 2

Completed

• Conditions: Cardiac Transplant; Cardiac Sarcoid; Myocarditis; Healthy Volunteers
• Interventions: Drug: Ferumoxytol

• Registration Number: NCT02319278
• Lead Sponsor: University of Edinburgh

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2014-12-03
• Study First Submitted QC: 2014-12-17
• Study First Posted: 2014-12-18
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-02
• Last Update Posted: 2017-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. 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

2. Age > 18 years.

Exclusion Criteria

1. Contraindication to magnetic resonance imaging scanning identified from magnetic resonance imaging safety questionnaire
2. Patients refusing or unable to give informed consent
3. Renal failure (estimated glomerular filtration rate <30 mL/min)
4. Polycythemia
5. 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.
6. Known allergy to dextran- or iron-containing compounds.
7. Diagnosis of myocardial infarction within 1 month.
8. Pregnancy or Breast-feeding.
9. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Myocarditis	Ferumoxytol	-
Cardiac sarcoid	Ferumoxytol	-
Cardiac Transplant	Ferumoxytol	-
Healthy Volunteers	Ferumoxytol	-

Primary Outcome Measures

Name	Time	Method
Assessment of Myocardial Cellular Inflammation.	1 year	Assessment of Myocardial Cellular Inflammation through the increase in R2\* value on post USPIO imaging versus baseline imaging.

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Royal Infirmary of Edinburgh; 🇬🇧 Edinburgh, United Kingdom

Golden Jubilee National Hospital; 🇬🇧 Glasgow, United Kingdom

Royal Brompton Hospital; 🇬🇧 London, United Kingdom