Feasibility Study of Arterial Stiffness in Hemodialysis Patients

NCT ID: NCT02196610

Last Updated: 2016-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

36 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-11-30

Study Completion Date

2016-03-31

Brief Summary

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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.

Detailed Description

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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:

i) 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.

Conditions

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End-Stage Renal Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Applanation tonometry

Intervention Type OTHER

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.

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.

Applanation tonometry

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type OTHER

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

* Age: \>18 years
* Able to provide informed consent


* 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

* 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


* 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 \[Daily cigarette consumption (\>15 cigarettes per day) adjusted by age, education level and other confounders has been found to be independently associated with the risk of hypertension\].
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The Ottawa Hospital

OTHER

Sponsor Role collaborator

University of Ottawa

OTHER

Sponsor Role collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kevin Burns, MD, CM

Role: STUDY_DIRECTOR

Ottawa Hospital Research Institute

Locations

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The Ottawa Hospital - Riverside campus

Ottawa, Ontario, Canada

Site Status

Countries

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Canada

References

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Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. doi: 10.1056/NEJMoa041031.

Reference Type BACKGROUND
PMID: 15385656 (View on PubMed)

Moody WE, Edwards NC, Chue CD, Ferro CJ, Townend JN. Arterial disease in chronic kidney disease. Heart. 2013 Mar;99(6):365-72. doi: 10.1136/heartjnl-2012-302818. Epub 2012 Oct 31.

Reference Type BACKGROUND
PMID: 23118349 (View on PubMed)

Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061.

Reference Type BACKGROUND
PMID: 20338492 (View on PubMed)

Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001 Feb 20;103(7):987-92. doi: 10.1161/01.cir.103.7.987.

Reference Type BACKGROUND
PMID: 11181474 (View on PubMed)

Karras A, Haymann JP, Bozec E, Metzger M, Jacquot C, Maruani G, Houillier P, Froissart M, Stengel B, Guardiola P, Laurent S, Boutouyrie P, Briet M; Nephro Test Study Group. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease. Hypertension. 2012 Dec;60(6):1451-7. doi: 10.1161/HYPERTENSIONAHA.112.197210. Epub 2012 Oct 22.

Reference Type BACKGROUND
PMID: 23090769 (View on PubMed)

Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension. 2005 Apr;45(4):592-6. doi: 10.1161/01.HYP.0000159190.71253.c3. Epub 2005 Mar 7.

Reference Type BACKGROUND
PMID: 15753232 (View on PubMed)

Boutouyrie P, Fliser D, Goldsmith D, Covic A, Wiecek A, Ortiz A, Martinez-Castelao A, Lindholm B, Massy ZA, Suleymanlar G, Sicari R, Gargani L, Parati G, Mallamaci F, Zoccali C, London GM. Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European Renal and Cardiovascular Medicine registry. Nephrol Dial Transplant. 2014 Feb;29(2):232-9. doi: 10.1093/ndt/gft309. Epub 2013 Sep 30.

Reference Type BACKGROUND
PMID: 24084326 (View on PubMed)

Frimodt-Moller M, Nielsen AH, Kamper AL, Strandgaard S. Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant. 2008 Feb;23(2):594-600. doi: 10.1093/ndt/gfm470. Epub 2007 Nov 7.

Reference Type BACKGROUND
PMID: 17989106 (View on PubMed)

Reference Values for Arterial Stiffness' Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values'. Eur Heart J. 2010 Oct;31(19):2338-50. doi: 10.1093/eurheartj/ehq165. Epub 2010 Jun 7.

Reference Type BACKGROUND
PMID: 20530030 (View on PubMed)

Pan CR, Schmaderer C, Roos M, von Eynatten M, Sollinger D, Lutz J, Heemann U, Baumann M. Comparing aortic stiffness in kidney transplant recipients, hemodialysis patients, and patients with chronic renal failure. Clin Transplant. 2011 Jul-Aug;25(4):E463-8. doi: 10.1111/j.1399-0012.2011.01462.x. Epub 2011 Apr 26.

Reference Type BACKGROUND
PMID: 21517999 (View on PubMed)

Giraudeau B, Mary JY. Planning a reproducibility study: how many subjects and how many replicates per subject for an expected width of the 95 per cent confidence interval of the intraclass correlation coefficient. Stat Med. 2001 Nov 15;20(21):3205-14. doi: 10.1002/sim.935.

Reference Type BACKGROUND
PMID: 11746313 (View on PubMed)

Cavalcante JL, Lima JA, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011 Apr 5;57(14):1511-22. doi: 10.1016/j.jacc.2010.12.017.

Reference Type BACKGROUND
PMID: 21453829 (View on PubMed)

Rodriguez RA, Cronin V, Ramsay T, Zimmerman D, Ruzicka M, Burns KD. Reproducibility of carotid-femoral pulse wave velocity in end-stage renal disease patients: methodological considerations. Can J Kidney Health Dis. 2016 Apr 1;3:20. doi: 10.1186/s40697-016-0109-6. eCollection 2016.

Reference Type DERIVED
PMID: 27042326 (View on PubMed)

Other Identifiers

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20140457

Identifier Type: -

Identifier Source: org_study_id

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