Clinical trial NCT02319278: DEtection of Cellular Inflammation With FERumoxytol in the HEART
Official title: DEtection of Cellular Inflammation With FERumoxytol in the HEART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cardiac Transplant
Cardiac Sarcoid
Myocarditis
Healthy Volunteers
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Royal Infirmary of Edinburgh
name: Golden Jubilee National Hospital
name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2014-12-18
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of Myocardial Cellular Inflammation.
timeFrame: 1 year
Secondary outcomes:
measure: Correlation of R2* values with circulating inflammatory markers
timeFrame: 1 year
measure: Does clinical condition correlate with inflammation seen on R2* maps. (assessed by reduction in R2* values)
timeFrame: 1 year
measure: Do higher R2* correlate with poorer outcome? (assessed by deterioration in ejection fraction or increase in late gadolinium enhancement)
timeFrame: 1 year
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: University of Edinburgh
name: Colin Stirrat, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stirrat CG, Alam S, MacGillivray TJ, Gray C, Dweck MR, Jones V, Wallace W, Payne JR, Prasad SK, Gardner RS, Petrie MC, Mirsadraee S, Henriksen P, Newby DE, Semple S. Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation. Open Heart. 2019 Oct 3;6(2):e001115. doi: 10.1136/openhrt-2019-001115. eCollection 2019.
citation: Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Dweck MR, Dibb K, Spath N, Payne JR, Prasad SK, Gardner RS, Mirsadraee S, Henriksen PA, Semple SI, Newby DE. Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis. Heart. 2018 Feb;104(4):300-305. doi: 10.1136/heartjnl-2017-311688. Epub 2017 Oct 6.
citation: Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Dweck MR, Raftis J, Jenkins WS, Wallace WA, Pessotto R, Lim KH, Mirsadraee S, Henriksen PA, Semple SI, Newby DE. Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction. Heart. 2017 Oct;103(19):1528-1535. doi: 10.1136/heartjnl-2016-311018. Epub 2017 Jun 22.
citation: Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Forsythe R, Dweck MR, Payne JR, Prasad SK, Petrie MC, Gardner RS, Mirsadraee S, Henriksen PA, Newby DE, Semple SI. Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T. J Cardiovasc Magn Reson. 2016 Jul 27;18(1):46. doi: 10.1186/s12968-016-0261-2.