Left Ventricular Fibrosis in Chronic Kidney Disease

Chronic Kidney Diseases Clinical Trial

— FibroCKD  

Official title:

Onset and Functional Consequences of Left Ventricular (LV) Fibrosis in Chronic Kidney

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03176862
• Other study ID #: UHB
• Status: Recruiting
• Phase: N/A
• First received: May 18, 2017
• Last updated: June 5, 2017
• Start date: September 2015
• Est. completion date: August 2018

Study information

• Verified date: June 2017
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: Manvir K Hayer, MBChB
• Phone: 07812732857
• Email: manvir.hayer[@]uhb.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to understand the onset an functional consequences of left ventricular interstitial fibrosis in patients with chronic kidney disease (stage 2 to 5), as well as assess whether transplantation results in a regression of cardiac fibrosis.Thus all patients will undergo: 1) a cardiac magnetic resonance imaging (MRI) scan to assess cardiac function and measure left ventricular interstitial fibrosis; 2) a cardiopulmonary stress echocardiogram to understand the functional consequences of fibrosis and rule out any underlying ischaemic heart disease; 3) a 24 hour holter monitor and electrocardiogram (ECG) to assess whether these patients are at higher risk of arrhythmia.

Description:

Aim and objectives:

The primary objective of this study is to test the following hypotheses:

i) Patients with early stage chronic kidney disease (CKD) exhibit diffuse LV fibrosis manifest by prolonged native myocardial T1 times and expansion of the extracellular volume (ECV) measured on MRI with a graded relationship to eGFR (stage of CKD), independent of blood pressure and arterial stiffness.

The secondary research objectives are to test the following hypotheses:

i) Prolonged native myocardial T1 times are associated with impaired diastolic function, altered arterial-ventricular interaction and impaired effort tolerance.

ii) Prolonged T1 times correlate with increases in serum biomarkers of collagen turnover associated with myocardial fibrosis that could be used to risk stratify individuals and enable targeted, personalized clinical care.

iii) Renal transplantation results in a regression of myocardial fibrosis as measured by T1 mapping.

DESIGN:

A cross-sectional analysis of 40 patients in each stage 2-5 CKD will be undertaken. These individuals will only be studied once (at baseline). In addition to this, at least 20 patients will be studied who are about to undergo a kidney transplant. These individuals will be studied at baseline (around the time of surgery), at 6 weeks post-operatively, and then 1 year post-operatively to assess the effect on renal transplantation on myocardial fibrosis.

SUBJECTS:

Patients will be recruited from the clinics run by University Hospitals Birmingham NHS Foundation Trust (UHB) with stages 2, 3, 4 and 5 CKD defined using eGFR calculated with the 4-variable 'Modification of Diet in Renal Disease' (MDRD) equation, with a minimum of two consecutive tests at least 90 days apart. Forty patients will be recruited per group of CKD. All study subjects will undergo a cardiac MRI scan, a cardiopulmonary exercise tests with stress echocardiogram, a 24-hour ECG holter monitor, and blood tests.

CONTROLS:

Forty healthy control subjects and forty hypertensive control subjects will be studied. All patients will undergo the identical research protocol to the CKD subjects, except they will not have a stress echocardiogram or an ECG holter monitor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: August 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• >18 years old

• CKD stage 2, 3, 4 and 5

Exclusion Criteria:

• Pregnancy

• Ischaemic heart disease (angina, ACS)

• Cerebral vascular disease

• Peripheral vascular disease

• Renovascular disease

• Diabetes mellitus

• Valvular heart disease (more than mild)

• Established diagnosis of heart failure

• Cannot have an MRI scan

Related Conditions & MeSH terms

• Cardio-Renal Syndrome
• Cardiomyopathies
• Chronic Kidney Diseases
• Fibrosis
• Kidney Diseases
• Myocardial Fibrosis
• Renal Insufficiency, Chronic
• Uraemic Cardiomyopathy

Intervention

Diagnostic Test:
• cardiac magnetic resonance scan
An MRI scan of the heart
• Cardiopulmonary exercise test with stress echocardiogram
An exercise bicycle test with echocardiogram done during the exercise.
• 24-hour ECG holter monitor
3 stickers attached to a small monitor are worn for 24 hours.
• 12-lead ECG
Can be done immediately by the bedside.
• Cardiopulmonary exercise test
An exercise bicycle test. No stress echocardiogram.

Biological:
• Blood test
20 mls of blood will be taken to measure routine laboratory tests and biomarkers of fibrosis.

Locations

Country	Name	City	State
United Kingdom	University Hospital Birmingham	Birmingham	West Midlands

Sponsors (2)

Lead Sponsor	Collaborator
Dr Manvir Kaur Hayer	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effect of eGFR on heart muscle scarring (measured from cardiac MRI using T1 times).	eGFR is a measurement of kidney function. Heart muscle scarring levels can be derived from cardiac MRI using a technique called T1 mapping. T1 maps of the heart will be acquired using cardiac MRI. eGFR will be measured from a blood tests, using the MDRD equation. The relationship between the measured T1 times and eGFR will be analysed using statistical tests.	One baseline visit only
Secondary	The relationship between prolonged myocardial T1 and diastolic function.	The following diastolic function parameters will be measured on echocardiography: E/A, deceleration time and E/e'.	One baseline visit only
Secondary	The relationship between prolonged myocardial T1 and effort tolerance.	The percent predicted peak oxygen uptake during exercise testing will be used as a surrogate marker of effort tolerance.	One baseline visit only
Secondary	The effect of renal transplantation on myocardial fibrosis.	Myocardial T1 times (cardiac MRI) and eGFR (blood testing) will best measured.	Baseline visit (pre-operation), then follow up at 6 weeks and 1 year.