Coronary Microvascular Dysfunction in Chronic Kidney Disease

Kidney Disease, Chronic Clinical Trial

— CRIB-FLOW  

Official title:

Coronary Microvascular Dysfunction in Chronic Kidney Disease: The Chronic Renal Impairment in Birmingham Coronary Flow Reserve (CRIB FLOW) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04014127
• Other study ID #: RRK6607
• Status: Recruiting
• Start date: May 7, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: July 2019
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: Ashwin Radhakrishnan, BM MRCP
• Phone: +447756931470
• Email: a.radhakrishnan[@]nhs.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational study assessing coronary microvascular function in healthy controls with normal kidney function, living kidney donors, pre-dialysis patients with chronic kidney disease stage 5 and patients on peritoneal dialysis.

Description:

The clinical syndrome of uraemic cardiomyopathy is prevalent in end stage renal disease and is associated with pathological cardiovascular changes including left ventricular hypertrophy, diastolic dysfunction and diffuse interstitial fibrosis. These combine to confer an elevated cardiovascular risk, including an increased risk of sudden cardiac death.

The cause of this increased cardiovascular risk is not clear but it is thought that coronary microvascular dysfunction may play a role. Coronary microvascular dysfunction is prevalent in many myocardial disease states, such as hypertrophic cardiomyopathy and heart failure with preserved ejection fraction, that share pathological similarities with uraemic cardiomyopathy.

Coronary flow reserve, a marker of coronary microvascular function, can be assessed non-invasively using echocardiography techniques. Previous studies have shown a reduction in coronary flow reserve in patients with chronic kidney disease. However, it is not clear if kidney donors - individuals who have a reduced kidney function but do not have progressive kidney disease - also demonstrate microvascular dysfunction. Similarly, although there is some evidence that patients on dialysis have improved coronary flow reserve compared to patients with pre-dialysis chronic kidney disease stage 5, there has been limited investigation into the role of peritoneal dialysis on coronary flow reserve.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Healthy control with normal renal function

• Living kidney donor who has donated >12 months prior to enrolment in study

• Chronic kidney disease stage 5 who are pre-dialysis or on peritoneal dialysis

• Able to provide written informed consent

Exclusion Criteria:

• Pregnancy

• Known ischaemic heart disease

• Diabetes mellitus

• Uncontrolled hypertension

• Evidence of 2nd or 3rd degree AV block or sick sinus syndrome in absence of a pacemaker

• History of allergic/adverse reaction to adenosine or Sonovue

• History of long QT syndrome

• Severe hypotension

• Significant valvular heart disease

• Significant chronic obstructive pulmonary disease or asthma with bronchospasm

• Unstable angina not controlled with medication

• Concurrent use of dipyridamole

• Decompensated heart failure

• Poor echo acoustic windows

• Chronic kidney disease stage 5 on haemodialysis

Related Conditions & MeSH terms

• Chronic Disease
• Kidney Disease, Chronic
• Kidney Diseases
• Myocardial Dysfunction
• Renal Insufficiency, Chronic

Intervention

Diagnostic Test:
• Coronary flow reserve assessment
Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.
• Sphygmocor
Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device
• Electrocardiogram
An electrocardiogram will be performed prior to administration of adenosine to ensure no resting conduction disease

Other:
• Blood test
Blood tests will be performed for markers of renal function, bone mineral metabolism and myocardial stretch and injury
• Urinary albumin/creatinine ratio
Urine will be analysed for albumin/creatinine ratio

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital	Birmingham

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pulse wave analysis	Augmentation index measured using the Sphygmocor device. Data will be presented as %.	One baseline visit
Other	Pulse wave velocity	Pulse wave velocity measured using the Sphygmocor device. Data will be presented as m/s	One baseline visit
Primary	Coronary flow reserve	Ultrasound-assessed coronary flow reserve. Data will be presented as a ratio (no unit) between maximal mean hyperemia flow velocity and baseline velocity	One baseline visit
Secondary	Myocardial blood flow	Ultrasound measurement of myocardial blood flow using myocardial contrast echocardiography. Data will be presented as dB/sec	One baseline visit
Secondary	Left ventricular ejection fraction	Echocardiogram assessed left ventricular ejection fraction by Simpson's biplane method. Data will be presented as %.	One baseline visit