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出境医 / 临床实验 / Coronary Microvascular Dysfunction in Chronic Kidney Disease (CRIB-FLOW)

Coronary Microvascular Dysfunction in Chronic Kidney Disease (CRIB-FLOW)

Study Description
Brief 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.

Condition or disease Intervention/treatment
Kidney Disease, Chronic Myocardial Dysfunction Diagnostic Test: Coronary flow reserve assessment Diagnostic Test: Sphygmocor Diagnostic Test: Electrocardiogram Other: Blood test Other: Urinary albumin/creatinine ratio

Detailed 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.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Coronary Microvascular Dysfunction in Chronic Kidney Disease: The Chronic Renal Impairment in Birmingham Coronary Flow Reserve (CRIB FLOW) Study
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : December 31, 2020
Arms and Interventions
Group/Cohort Intervention/treatment
Controls
25 controls with preserved renal function
Diagnostic Test: Coronary flow reserve assessment
Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.

Diagnostic Test: Sphygmocor
Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device

Diagnostic Test: 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

Other: Urinary albumin/creatinine ratio
Urine will be analysed for albumin/creatinine ratio

Kidney Donors
25 living kidney donors who have donated a kidney at least 12 months prior to enrollment in the study.
Diagnostic Test: Coronary flow reserve assessment
Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.

Diagnostic Test: Sphygmocor
Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device

Diagnostic Test: 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

Other: Urinary albumin/creatinine ratio
Urine will be analysed for albumin/creatinine ratio

Pre-dialysis
25 patients with pre-dialysis chronic kidney disease stage 5
Diagnostic Test: Coronary flow reserve assessment
Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.

Diagnostic Test: Sphygmocor
Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device

Diagnostic Test: 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

Other: Urinary albumin/creatinine ratio
Urine will be analysed for albumin/creatinine ratio

Peritoneal dialysis
25 patients with chronic kidney disease stage 5 undergoing peritoneal dialysis
Diagnostic Test: Coronary flow reserve assessment
Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.

Diagnostic Test: Sphygmocor
Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device

Diagnostic Test: 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

Other: Urinary albumin/creatinine ratio
Urine will be analysed for albumin/creatinine ratio

Outcome Measures
Primary Outcome Measures :
  1. Coronary flow reserve [ Time Frame: One baseline visit ]
    Ultrasound-assessed coronary flow reserve. Data will be presented as a ratio (no unit) between maximal mean hyperemia flow velocity and baseline velocity


Secondary Outcome Measures :
  1. Myocardial blood flow [ Time Frame: One baseline visit ]
    Ultrasound measurement of myocardial blood flow using myocardial contrast echocardiography. Data will be presented as dB/sec

  2. Left ventricular ejection fraction [ Time Frame: One baseline visit ]
    Echocardiogram assessed left ventricular ejection fraction by Simpson's biplane method. Data will be presented as %.


Other Outcome Measures:
  1. Pulse wave analysis [ Time Frame: One baseline visit ]
    Augmentation index measured using the Sphygmocor device. Data will be presented as %.

  2. Pulse wave velocity [ Time Frame: One baseline visit ]
    Pulse wave velocity measured using the Sphygmocor device. Data will be presented as m/s


Biospecimen Retention:   Samples Without DNA
Serum and plasma will be stored for future biomarker analysis including N terminal pro brain natriuretic peptide and troponin.

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients attending University Hospitals Birmingham.
Criteria

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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Ashwin Radhakrishnan, BM MRCP +447756931470 a.radhakrishnan@nhs.net

Locations
Layout table for location information
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Ashwin Radhakrishnan, BM MRCP    +447756931470    a.radhakrishnan@nhs.net   
Principal Investigator: Jonathan N Townend, MD FRCP FESC         
Sponsors and Collaborators
University Hospital Birmingham NHS Foundation Trust
Investigators
Layout table for investigator information
Principal Investigator: Jonathan N Townend, MD FRCP FESC University Hospitals Birmingham
Tracking Information
First Submitted Date July 8, 2019
First Posted Date July 10, 2019
Last Update Posted Date July 10, 2019
Actual Study Start Date May 7, 2019
Estimated Primary Completion Date August 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 8, 2019)
Coronary flow reserve [ Time Frame: One baseline visit ]
Ultrasound-assessed coronary flow reserve. Data will be presented as a ratio (no unit) between maximal mean hyperemia flow velocity and baseline velocity
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: July 8, 2019)
  • Myocardial blood flow [ Time Frame: One baseline visit ]
    Ultrasound measurement of myocardial blood flow using myocardial contrast echocardiography. Data will be presented as dB/sec
  • Left ventricular ejection fraction [ Time Frame: One baseline visit ]
    Echocardiogram assessed left ventricular ejection fraction by Simpson's biplane method. Data will be presented as %.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 8, 2019)
  • Pulse wave analysis [ Time Frame: One baseline visit ]
    Augmentation index measured using the Sphygmocor device. Data will be presented as %.
  • Pulse wave velocity [ Time Frame: One baseline visit ]
    Pulse wave velocity measured using the Sphygmocor device. Data will be presented as m/s
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Coronary Microvascular Dysfunction in Chronic Kidney Disease
Official Title Coronary Microvascular Dysfunction in Chronic Kidney Disease: The Chronic Renal Impairment in Birmingham Coronary Flow Reserve (CRIB FLOW) Study
Brief 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.
Detailed 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.

Study Type Observational
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Serum and plasma will be stored for future biomarker analysis including N terminal pro brain natriuretic peptide and troponin.
Sampling Method Non-Probability Sample
Study Population Patients attending University Hospitals Birmingham.
Condition
  • Kidney Disease, Chronic
  • Myocardial Dysfunction
Intervention
  • Diagnostic Test: Coronary flow reserve assessment
    Coronary flow reserve will be assessed using Doppler transthoracic echocardiograpy and myocardial contrast echocardiography.
  • Diagnostic Test: Sphygmocor
    Pulse wave analysis and pulse wave velocity will be assessed using the Sphygmocor device
  • Diagnostic Test: 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
  • Other: Urinary albumin/creatinine ratio
    Urine will be analysed for albumin/creatinine ratio
Study Groups/Cohorts
  • Controls
    25 controls with preserved renal function
    Interventions:
    • Diagnostic Test: Coronary flow reserve assessment
    • Diagnostic Test: Sphygmocor
    • Diagnostic Test: Electrocardiogram
    • Other: Blood test
    • Other: Urinary albumin/creatinine ratio
  • Kidney Donors
    25 living kidney donors who have donated a kidney at least 12 months prior to enrollment in the study.
    Interventions:
    • Diagnostic Test: Coronary flow reserve assessment
    • Diagnostic Test: Sphygmocor
    • Diagnostic Test: Electrocardiogram
    • Other: Blood test
    • Other: Urinary albumin/creatinine ratio
  • Pre-dialysis
    25 patients with pre-dialysis chronic kidney disease stage 5
    Interventions:
    • Diagnostic Test: Coronary flow reserve assessment
    • Diagnostic Test: Sphygmocor
    • Diagnostic Test: Electrocardiogram
    • Other: Blood test
    • Other: Urinary albumin/creatinine ratio
  • Peritoneal dialysis
    25 patients with chronic kidney disease stage 5 undergoing peritoneal dialysis
    Interventions:
    • Diagnostic Test: Coronary flow reserve assessment
    • Diagnostic Test: Sphygmocor
    • Diagnostic Test: Electrocardiogram
    • Other: Blood test
    • Other: Urinary albumin/creatinine ratio
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 8, 2019)
100
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2020
Estimated Primary Completion Date August 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Ashwin Radhakrishnan, BM MRCP +447756931470 a.radhakrishnan@nhs.net
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT04014127
Other Study ID Numbers RRK6607
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Anna Price, University Hospital Birmingham NHS Foundation Trust
Study Sponsor University Hospital Birmingham NHS Foundation Trust
Collaborators Not Provided
Investigators
Principal Investigator: Jonathan N Townend, MD FRCP FESC University Hospitals Birmingham
PRS Account University Hospital Birmingham NHS Foundation Trust
Verification Date July 2019