Validating Novel, Non-contrast Cardiac MRI Imaging in Haemodialysis Patients

End Stage Kidney Disease Clinical Trial

— CONFIRM  

Official title:

Validating the Accuracy of Novel, Non-contrast, Cardiac Magnetic resOnaNce Imaging in Defining Myocardial FIbRosis in Patients With End-stage Renal Disease on haeModialysis: the CONFIRM Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03586518
• Other study ID #: 0674
• Status: Recruiting
• Start date: November 3, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2022
• Source: University of Leicester
• Contact: James Burton, DM, FRCP
• Phone: +44 (0)116 2588043
• Email: jb343[@]le.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There are currently no good ways of measuring levels of scarring in the hearts of patients with advanced kidney disease and patients on dialysis, although recent research has shown a new cardiac MRI technique, called native T1 mapping, may provide a solution to this. To assess the accuracy of this novel technique in dialysis patients, it is essential to undertake a study which compares native T1 mapping to actual levels of scarring in the hearts of patients on dialysis.

Description:

Native T1 mapping is a novel, non-contrast, cardiac MRI technique that characterises myocardial tissue by exploiting the different water content of tissues. It correlates well with histo-pathological levels of myocardial fibrosis in diseases of pressure overload such as aortic stenosis. There is growing evidence to demonstrate the potential of native T1 mapping as an imaging biomarker of myocardial fibrosis in patients with ESRD; myocardial native T1 values are higher in patients with ESRD than controls, and associate with measures of myocardial strain and circulating markers of cardiac dysfunction. Although native T1 times are affected by water content of tissues, our group has shown that native T1 times are not influenced by clinical changes in fluid status in HD patients and that the inter-study reproducibility and intra- and inter-observer variability of native T1 are outstanding. Native T1 mapping is a promising, non-invasive imaging biomarker of myocardial fibrosis in patients with advanced renal disease. It is essential that the technique is validated against histology before further use in clinical studies. The aim of this study is to directly assess the relationship between native T1 mapping and levels of MF examined at post-mortem in haemodialysis patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prevalent haemodialysis patient (more than 3 months)
• Active on the supportive care register with anticipated death in the subsequent 12 months
• Able to give informed consent
• Consent to donation of heart for research following death
• Able to understand written and verbal explanations in English

Exclusion Criteria:

• Contraindication to MRI scan (e.g. pacemaker, incompatible metallic implants, claustrophobia)
• Patients with expected or potential infiltrative cardiomyopathy (e.g. amyloidosis)
• Unable to give informed consent
• Unable to understand written and verbal explanations in English

Related Conditions & MeSH terms

• End Stage Kidney Disease
• Fibrosis
• Fibrosis Myocardial
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Diagnostic Test:
• Cardiac MRI scan
A non-contrast cardiac MRI (CMR) scan at 3-Tesla platform (Skyra, Siemens Medical Imaging, Erlangen, Germany). This non-contrast CMR scan will principally determine: Left ventricular (LV) mass and volumes/ejection fraction and; fibrosis using T1 mapping.
• Echocardiogram
Assessments will include: LV size and function as per the American Society of Echocardiography guidelines. In addition specific focus will be paid end-diastolic integrated backscatter measurements.

Procedure:
• Cardiac explantation
A limited post-mortem will be performed to retrieve patients' hearts for preparation and storage at St George's University, London where direct comparison will be made between levels of scarring seen directly under the microscope between that on the MRI scans.

Diagnostic Test:
• 48-Hour continuous cardiac monitoring
Attach continuous Holter monitor (Schiller, medilog®AR12 plus/AR4 plus/FD5 plus, Baar, Switzerland) that will start before dialysis and terminate just before the subsequent dialysis treatment 48h later.
• Blood samples
Collect blood samples from the arterial needle before dialysis. Approximately 30 millilitres of blood will be collected and then be pipetted into cryotubes and frozen at -80°C in an electronically monitored freezer for analysis in batches throughout the study. These samples will be used to investigate the relationship between circulating biomarkers of fibrosis, the MRI scans and the histological samples.

Locations

Country	Name	City	State
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester	Leicestershire

Sponsors (3)

Lead Sponsor	Collaborator
University of Leicester	St George's, University of London, University Hospitals, Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between MRI and histological measures of cardiac fibrosis	To assess the correlation between native T1 values measured using cardiac MRI in haemodialysis patients approaching the end of their lives, with histological samples analysed post-mortem.	Cardiac MRI performed within 12-months of histological samples obtained post-mortem
Secondary	Accuracy of MRI versus ECHO in the measurement of cardiac fibrosis	Relationship between integrated backscatter (measured with echocardiography) and levels of myocardial fibrosis on histology measured at post-mortem.	Echocardiograms performed within 12-months of histological samples obtained post-mortem
Secondary	Relationship between cardiac fibrosis and heart rhythm	Relationship between continuous Holter-monitor data and levels of myocardial fibrosis on histology measured at post-mortem.	Continuous Holter recording performed within 12-months of histological samples obtained post-mortem
Secondary	Correlation between cardiac fibrosis and relevant circulating biomarkers	Relationship between humoral markers of cardiac dysfunction of fibrosis and levels of myocardial fibrosis on histology measured at post-mortem	Samples collected within 12-months of histological samples obtained post-mortem
Secondary	Additional cardiac MRI techniques and the measurement of cardiac fibrosis	The relationship between additional, non-contrast CMR techniques and histology at post-mortem	Cardiac MRI performed within 12-months of histological samples obtained post-mortem