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

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ClinicalTrials.gov Identifier: NCT03586518
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : January 31, 2020
Sponsor:
Collaborators:
University Hospitals, Leicester
St George's, University of London
Information provided by (Responsible Party):
University of Leicester

Brief 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.

Condition or disease Intervention/treatment
End Stage Kidney Disease Fibrosis Myocardial Diagnostic Test: Cardiac MRI scan Diagnostic Test: Echocardiogram Procedure: Cardiac explantation Diagnostic Test: 48-Hour continuous cardiac monitoring Diagnostic Test: Blood samples

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 9 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : November 3, 2019
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Haemodialysis patients

The plans for patient recruitment were developed in partnership with our local haemodialysis patient participation and involvement group. Patients will be identified from the supportive care register established for haemodialysis patients in Leicester in 2008.

Inclusion:

  • 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:

  • 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
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.

Other Name: CMR

Diagnostic Test: 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.
Other Name: ECHO

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.
Other Name: Holter

Diagnostic Test: 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.




Primary Outcome Measures :
  1. Correlation between MRI and histological measures of cardiac fibrosis [ Time Frame: Cardiac MRI performed within 12-months of histological samples obtained post-mortem ]
    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.


Secondary Outcome Measures :
  1. Accuracy of MRI versus ECHO in the measurement of cardiac fibrosis [ Time Frame: Echocardiograms performed within 12-months of histological samples obtained post-mortem ]
    Relationship between integrated backscatter (measured with echocardiography) and levels of myocardial fibrosis on histology measured at post-mortem.

  2. Relationship between cardiac fibrosis and heart rhythm [ Time Frame: Continuous Holter recording performed within 12-months of histological samples obtained post-mortem ]
    Relationship between continuous Holter-monitor data and levels of myocardial fibrosis on histology measured at post-mortem.

  3. Correlation between cardiac fibrosis and relevant circulating biomarkers [ Time Frame: Samples collected within 12-months of histological samples obtained post-mortem ]
    Relationship between humoral markers of cardiac dysfunction of fibrosis and levels of myocardial fibrosis on histology measured at post-mortem

  4. Additional cardiac MRI techniques and the measurement of cardiac fibrosis [ Time Frame: Cardiac MRI performed within 12-months of histological samples obtained post-mortem ]
    The relationship between additional, non-contrast CMR techniques and histology at post-mortem


Biospecimen Retention:   Samples With DNA
Patient hearts explanted post-mortem


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
The plans for patient recruitment were developed in partnership with our local haemodialysis patient participation and involvement group. Patients will be identified by means of a well established supportive care register for haemodialysis patients. These patients, and often their families, have engaged in discussion about end-of-life care, including discussions about limitations on care and preferred place of death.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03586518


Contacts
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Contact: James Burton, DM, FRCP +44 (0)116 2588043 jb343@le.ac.uk
Contact: Matthew Graham-Brown, MBChB, MRCP +44 (0)116 2588043 mgb23@le.ac.uk

Locations
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United Kingdom
University Hospitals of Leicester NHS Trust Recruiting
Leicester, Leicestershire, United Kingdom, LE5 4PW
Contact: James Burton, FRCP    01162588043    jb343@le.ac.uk   
Sub-Investigator: Matthew Graham-Brown, MRCP         
Sponsors and Collaborators
University of Leicester
University Hospitals, Leicester
St George's, University of London
Investigators
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Principal Investigator: James Burton, DM, FRCP Associate Professor in Renal Medicine
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT03586518    
Other Study ID Numbers: 0674
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The full study protocol will be published online, open access.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: The protocol will be published within 12 months of registration.
Access Criteria: Open access.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Leicester:
Cardiac MRI
Hemodialysis
Myocardial Fibrosis
Myocardial Inflammation
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Fibrosis
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency