MRI Assessment of Myocardial Fibrosis Associated With Monocyte Phenotype in End Stage Renal Failure

NCT03857633 | Withdrawn

• 2 other identifiers: 18HH4615221424
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Firstly, this study aims to understand how cardiac fibrosis mediated by inflammatory microvascular disease evolves during advanced chronic kidney disease and end stage renal failure and importantly how this changes with commencement on renal replacement therapy (haemodialysis and peritoneal dialysis) using sequential cardiac MRI imaging. This method of imaging is non-invasive, provides significantly more data than echocardiography, is reproducible and accurate, has been validated in numerous studies and does not involve exposure to ionising radiation. Secondly, this study aims to examine the changes in monocyte subsets and biochemical profile in peripheral blood prior to, during and after commencement on renal replacement therapy. The investigators hypothesis would be that renal failure causes alteration in monocyte subset phenotype resulting in increased circulating inflammatory monocytes (human CD14high CD16high), initiating pro-inflammatory cytokine expression and thereby accelerating inflammatory cardiovascular disease and development of myocardial fibrosis.

Conditions

Myocardial Fibrosis; End Stage Renal Failure on Dialysis; Chronic Kidney Disease, Stage IV (Severe); Chronic Kidney Disease Stage V; Heart Failure

Keywords

Cardiac MRI; Myocardial Fibrosis; End Stage Renal Failure; Monocyte Subsets; Renal Replacement Therapy

Outcome Measures

Primary Outcomes (1)

• The development and modulation of myocardial fibrosis and change in cardiac function with CKD progression and commencement on renal replacement therapy

  Cardiac MRI assessment of the evolution of myocardial fibrosis and cardiac function using sequential contrast enhanced CMR imaging (at three time points) during transition to end stage renal failure and commencement on renal replacement therapy

  18 Months

Secondary Outcomes (1)

• Change in monocyte subsets and biochemical profile in peripheral blood with CKD progression and commencement on renal replacement therapy

  18 Months

Study Arms (3)

Pre Dialysis (CKD Stage 4/5)

Patients recruited from low clearance clinic with advanced CKD (stage 4/5). Patients will undergo Cardiac MRI 1 - With Gadolinium Contrast at the time of recruitment and Cardiac MRI 2 - With Gadolinium Contrast at time of commencement on renal replacement therapy. Patients will have Peripheral Whole Blood Samples taken at defined intervals.

Diagnostic Test: Cardiac MRI 1 - With Gadolinium Contrast; Diagnostic Test: Cardiac MRI 2 - With Gadolinium Contrast; Diagnostic Test: Peripheral Whole Blood Samples

Haemodialysis Dialysis (CDK Stage 5d)

Patients started on Haemodialysis will have Cardiac MRI 3 - With Gadolinium Contrast after 6 months of therapy. Patients will have Peripheral Whole Blood Samples taken at defined intervals.

Diagnostic Test: Cardiac MRI 3 - With Gadolinium Contrast; Diagnostic Test: Peripheral Whole Blood Samples

Peritoneal Dialysis (CDK Stage 5d)

Patients started on Peritoneal Dialysis will have Cardiac MRI 3 - Without Gadolinium Contrast after 6 months of therapy. Patients will have Peripheral Whole Blood Samples taken at defined intervals.

Diagnostic Test: Cardiac MRI 3 - Without Gadolinium Contrast; Diagnostic Test: Peripheral Whole Blood Samples

Interventions

Cardiac MRI 1 - With Gadolinium Contrast DIAGNOSTIC_TEST

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

Pre Dialysis (CKD Stage 4/5)

Cardiac MRI 2 - With Gadolinium Contrast DIAGNOSTIC_TEST

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

Pre Dialysis (CKD Stage 4/5)

Cardiac MRI 3 - Without Gadolinium Contrast DIAGNOSTIC_TEST

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps. During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

Peritoneal Dialysis (CDK Stage 5d)

Cardiac MRI 3 - With Gadolinium Contrast DIAGNOSTIC_TEST

Cines for cardiac function and volumes, T2 myomaps, Resting perfusion and strain analysis, Tagging (strain), T1 myomaps, Late gadolinium enhancement During the MRI scan participants would be required perform a short period of low intensity exercise involving peddling on an adapted cycle for 10-15 minutes to provide additional data on cardiac function under exertion.

Haemodialysis Dialysis (CDK Stage 5d)

Peripheral Whole Blood Samples DIAGNOSTIC_TEST

20ml EDTA whole blood samples - collected sequentially during study - max 8 time points

Haemodialysis Dialysis (CDK Stage 5d); Peritoneal Dialysis (CDK Stage 5d); Pre Dialysis (CKD Stage 4/5)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced and progressive Chronic Kidney Disease (Stage 4/5) - under low clearance follow-up who are expected to start renal replacement therapy (either haemodialysis or peritoneal dialysis) within 6 months.

You may qualify if:

• Patients with a diagnosis of Chronic Kidney Disease stage 4 and above
• Patients with a progressive decline in renal function with a expectation to require future renal replacement therapy or currently on renal replacement therapy (Haemodialysis or Peritoneal Dialysis)
• Access for haemodialysis planned via tunnelled central venous catheter

You may not qualify if:

• Age under eighteen
• Patients with a diagnosis of Diabetes Mellitus
• Untreated macrovascular cardiac disease or Acute Coronary syndrome within 6 months of recruitment
• Previous or current treatment with immunosuppressive/modulatory therapy
• Current Malignancy
• Current use of Metformin
• Pregnancy
• Contraindication to MRI Imaging
• Patients lacking capacity or unable to consent and non-English language speakers
• Immediate modality switch after commencement on renal replacement therapy i.e. transplantation
• Plan for treatment centre change/move outside of Imperial College Healthcare NHS Trust following commencement on renal replacement therapy
• Patients currently participating in an active CTIMP trial

Sponsors & Collaborators

• Imperial College London: lead
• National Institute for Health Research, United Kingdom: collaborator
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood and Serum Samples

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Heart Failure

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Study Officials

• Neill Duncan, MBBS FRCP

  Imperial College Healthcare NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: February 28, 2019
• Study Start: February 1, 2019
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: October 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)