Feasibility Study of Arterial Stiffness in Hemodialysis Patients

End-Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02196610
• Other study ID #: 20140457
• Status: Terminated
• Phase: N/A
• First received: July 18, 2014
• Last updated: April 28, 2016
• Start date: November 2014
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Observational

Clinical Trial 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.

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:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 36
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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].

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

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.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital - Riverside campus	Ottawa	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	The Ottawa Hospital, University of Ottawa

Country where clinical trial is conducted

Canada, 

References & Publications (12)

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. Review. — View Citation

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. Review. — View Citation

Frimodt-Møller 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. Epub 2007 Nov 7. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2008;18(4):4. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Pannier B, Guérin 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. Epub 2005 Mar 7. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Normative Pulse Wave Velocity Values	We will calculate the mean, standard deviation and 95% confidence interval of the pulse wave velocity values and Augmentation index in our defined populations.	11 months	No
Primary	Reliability of carotid-femoral Pulse Wave Velocity measurements	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.	1 week	No
Secondary	Accuracy of the carotid-femoral Pulse Wave Velocity measurements	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	1 week	No
Secondary	Subject satisfaction and procedure discomfort	This will be accomplished by surveying subjects at the end of the testing procedure using a Likert-type questionnaire	1 week	No
Secondary	Recruitment Efficacy	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	11 months	No