Feasibility Study of Arterial Stiffness in Hemodialysis Patients

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT02196610

Collaborator

The Ottawa Hospital (Other), University of Ottawa (Other)

Enrollment

Location

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

People with kidney failure have a higher chance of getting disease in the blood vessels and this result in a decreased elasticity of the arteries of their body which make them very stiff or hard. It appears that stiffer arteries with a decreased elasticity increase the risk of stroke and heart disease. A novel way to know the stiffness of blood vessels is by a method called "applanation tonometry", which measures the "pulse wave velocity" of major blood vessels such as the aorta, carotid and femoral arteries. The purpose of our study is to determine if we can measure arterial stiffness reliably and accurately using this method in healthy people and in people with kidney failure receiving hemodialysis treatments at our centre. Also, we would like to know how stiff these arteries in healthy people are. If we demonstrate that the method is reliable and accurate in these 2 groups of participants at our centre, a future larger study is planned to determine if we can use measures of arterial stiffness to evaluate the risk of stroke and heart disease in people with kidney failure receiving hemodialysis. The research study will take place at the Ottawa Hospital-Riverside Campus.

Condition or Disease	Intervention/Treatment	Phase
End-Stage Renal Disease	Other: Applanation tonometry

Detailed Description

Background:

Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Arterial stiffness measured by pulse-wave velocity (PWV) has been identified as an independent predictor of fatal CV events in these patients. Our long-term goal is to study the impact of interventions that decrease progressive arterial stiffness on CV mortality in ESRD patients. Thus, we postulate that measurements of PWV during these interventions will predict CV outcome. Before studying this relationship, establishing the feasibility of PWV measurements at our centre is necessary.

Objectives:

To demonstrate the reliability and accuracy of arterial PWV measurements in healthy subjects and patients with ESRD at our centre, ii) To assess subject satisfaction and level of discomfort associated with the testing procedure, iii) To characterize normative values for the PWV in our two subject groups, and iv) To determine the feasibility of recruitment of patients with ESRD, as a pre-requisite for a larger trial focused on CV outcomes.

Methods:

PWV will be measured consecutively by 2 research assistants in: a) a group of 20 healthy subjects; and b) a group of 20 patients with ESRD on chronic hemodialysis at The Ottawa Hospital. Two consecutive sets of PWV measurements with a time-interval of 1 week (± 2 days) will be obtained in the healthy and ESRD groups (pre-hemodialysis, between 2 consecutive mid-week hemodialysis sessions). To determine the impact of hemodialysis on PWV measures, in a sub-group of 10 ESRD subjects measurements will be taken before and after hemodialysis. The order of testing by the 2 assistants will be randomized.

Study Design

Study Type:

Observational

Actual Enrollment :

36 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Arterial Stiffness in Healthy Subjects and Patients With End-Stage- Renal Disease: A Feasibility Study

Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
HEALTHY SUBJECTS group A group of 20 healthy staff volunteers identified from the Division of Nephrology, Dept. of Medicine and the Kidney Research Centre at the Ottawa Hospital Research Institute will be invited to participate. Measurements of arterial stiffness will be performed by Applanation tonometry. Healthy status will be defined by a self-reporting questionnaire obtained over the phone prior to enrolment and 2 subsequent non-invasive measurements of arterial blood pressure (BP) prior to testing. Subjects will be included if diastolic BP is ≤ 90 mm Hg and systolic BP ≤ 140 mm Hg on 2 consecutive measurements.	Other: Applanation tonometry Two consecutive sets of carotid-femoral Pulse Wave Velocity (PWV) measurements by Applanation tonometry with a time-interval of 1 week will be obtained (1 week ± 2 days). Two research assistants will each perform a carotid-femoral-PWV measurement at each time point with the testing order randomized. Other Names: carotid-femoral Pulse wave velocity (c-f-PWV)
END-STAGE RENAL DISEASE (ESRD) group A group of 20 patients with stage 5 Chronic Kidney Disease (estimated glomerular filtration rate <15 ml/min/m2), who attend chronic hemodialysis treatments at The Ottawa Hospital (TOH) will be invited to participate. Measurements of arterial stiffness will be performed in this group by Applanation tonometry.	Other: Applanation tonometry Two consecutive sets of carotid-femoral Pulse Wave Velocity (PWV) measurements by Applanation tonometry with a time-interval of 1 week will be obtained (1 week ± 2 days). Two research assistants will each perform a carotid-femoral-PWV measurement at each time point with the testing order randomized. Other Names: carotid-femoral Pulse wave velocity (c-f-PWV)

Arm

Intervention/Treatment

HEALTHY SUBJECTS group

A group of 20 healthy staff volunteers identified from the Division of Nephrology, Dept. of Medicine and the Kidney Research Centre at the Ottawa Hospital Research Institute will be invited to participate. Measurements of arterial stiffness will be performed by Applanation tonometry. Healthy status will be defined by a self-reporting questionnaire obtained over the phone prior to enrolment and 2 subsequent non-invasive measurements of arterial blood pressure (BP) prior to testing. Subjects will be included if diastolic BP is ≤ 90 mm Hg and systolic BP ≤ 140 mm Hg on 2 consecutive measurements.

Other: Applanation tonometry

Two consecutive sets of carotid-femoral Pulse Wave Velocity (PWV) measurements by Applanation tonometry with a time-interval of 1 week will be obtained (1 week ± 2 days). Two research assistants will each perform a carotid-femoral-PWV measurement at each time point with the testing order randomized.

Other Names:

carotid-femoral Pulse wave velocity (c-f-PWV)

END-STAGE RENAL DISEASE (ESRD) group

A group of 20 patients with stage 5 Chronic Kidney Disease (estimated glomerular filtration rate <15 ml/min/m2), who attend chronic hemodialysis treatments at The Ottawa Hospital (TOH) will be invited to participate. Measurements of arterial stiffness will be performed in this group by Applanation tonometry.

Other: Applanation tonometry

Other Names:

carotid-femoral Pulse wave velocity (c-f-PWV)

Outcome Measures

Primary Outcome Measures

Reliability of carotid-femoral Pulse Wave Velocity measurements [1 week]
We will estimate the Pulse Wave Velocity differences and the intra-class correlation coefficient (ICC) between the 2 examinations (test-retest) recorded in the same subject 1 week apart. We will also estimate the examiner's reliability by the inter-rater agreement through the ICC and limits of agreement.

Secondary Outcome Measures

Accuracy of the carotid-femoral Pulse Wave Velocity measurements [1 week]
This will be estimated by calculating the mean, standard deviation and 95% confidence interval of the Pulse Wave Velocity differences between our healthy group and the age-adjusted mean values from a historical healthy control group
Subject satisfaction and procedure discomfort [1 week]
This will be accomplished by surveying subjects at the end of the testing procedure using a Likert-type questionnaire
Recruitment Efficacy [11 months]
We will assess the proportion of patients with End-Stage Renal disease (ESRD) who consented to the testing procedure relative to the number of eligible and screened participants

Other Outcome Measures

Normative Pulse Wave Velocity Values [11 months]
We will calculate the mean, standard deviation and 95% confidence interval of the pulse wave velocity values and Augmentation index in our defined populations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

HEALTHY SUBJECT GROUP

Inclusion criteria:

Age: >18 years
Able to provide informed consent

Exclusion criteria

History of cardiovascular disease and/or hypertension (blood pressure >140/90 mm Hg)
History of diabetes mellitus
History of liver or kidney disease, cancer and/or any lymphoproliferative disease
Currently receiving medication for any medical condition or illness
Body Mass Index (BMI) ≥ 30 Kg/m2
Pregnancy
Any condition that limits functional ability and precludes participation
Current smoker (>15 cigarettes per day) in the last 6 months.
Former smoker (> 20 cigarettes per day) who stopped smoking < 2 years ago.
Excessive alcohol intake (men >14 drinks per week; women: > 9 drinks per week).
Psychoactive or performance-enhancing drug abuse.

END-STAGE RENAL DISEASE (ESRD) GROUP

Inclusion Criteria:

Adult patient (age: >18 years) with ESRD (estimated glomerular filtration rate: <15 ml/min/m2)
Receiving hemodialysis treatments, with no expected renal recovery
Having received regular in-Centre Hemodialysis at TOH for at least the past 3 weeks
Able to provide informed consent.

Exclusion Criteria:

Atrial fibrillation (as it frequently results in transient or persistent rapid heart rates and these changes overestimate aortic stiffness).
Active cancer or history of cancer in the past 5 years.
Pregnancy
Any condition that limit the patient's ambulatory ability and preclude participation on this basis
Mechanical, bioprosthetic heart valves or mechanical assisting devices (these conditions may change myocardial stiffness and the volumetric properties of the left ventricle leading to diastolic dysfunction and these physiologic changes may modify the waveforms of the cf- APWV).
Pre-dialysis systolic blood pressure ≥ 200 mm Hg recorded in the last 6 dialysis treatments (2 weeks).
Inability to measure blood pressure in at least one arm.
Current smoker (>15 cigarettes per day) in the last 6 months [Daily cigarette consumption (>15 cigarettes per day) adjusted by age, education level and other confounders has been found to be independently associated with the risk of hypertension].