Exercise and Vascular Parameters in Hemodialysis

Study Overview
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Brief Summary
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Arterial calcification is very common in the incident hemodialysis population, ranging 71-83%.Given that cardiovascular disease is a major cause of mortality in the hemodialysis population, medial arterial calcification may contribute through increased risk of sudden death and congestive heart failure. Applanation tonometry is the method of choice to measure pulse wave velocity and pulse wave analysis. The primary objective will be to assess the effect of a 16 week exercise program on aortic pulse wave velocity as the vascular parameter and gait speed as the physical functioning parameter. The secondary objectives will assess the effect of the exercise program on ultrafiltration rates, weight, SBP, DBP, BNP, hsTroponin, serum calcium, phosphate, albumin, glucose, LDL, HDL, TG, glycated hemoglobin, hemoglobin, CRP, micro RNAs (21, 126, 133, 146a, 221/222 and 210) and hospitalizations.

Detailed Description
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The investigators propose a pilot project to assess the effect of a 16 week aerobic exercise program on arterial stiffness and cardiovascular risk in the hemodialysis population. The primary objective will be to assess the effect of a 16 week exercise program on aortic pulse wave velocity as the vascular parameter and gait speed as the physical functioning parameter. The secondary objectives will assess the effect of the exercise program on ultrafiltration rates, weight, SBP, DBP, BNP, hsTroponin, serum calcium, phosphate, albumin, glucose, LDL, HDL, TG, glycated hemoglobin, hemoglobin, CRP, micro RNAs (21, 126, 133, 146a, 221/222 and 210) and hospitalizations. Study Design: Randomized-controlled study of end stage renal disease patients between the age of 18 and 90 years to assess the effect of exercise on arterial stiffness. Our aim is to have 23 patients in both groups. The study period will be 24 weeks-4 weeks for recruitment, 16 weeks for the intervention and 4 weeks for data collection and analysis. The protocol will be submitted to the MUHC Research Ethics Board. The following outcomes are of interest: change in gait speed before and after the exercise program change in pulse wave velocity before and after the exercise program change in BNP, blood pressure, dialysis ultrafiltration, hemoglobin, micro RNAs before and after the exercise program

Official Title
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Aerobic Exercise and Vascular Hemodynamic Parameters Among Prevalent Hemodialysis Population

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Behavioral: Aerobic Exercise program
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18-95 years Able to comply with the study procedures and medication Written informed consent given On a stable in-center hemodialysis regimen (at least 3 times per week) for ≥ 12 weeks prior to recruitment Cardiac evaluation within the year with adequate cardiac function to be able to undergo the exercise program Exclusion Criteria: Participation in any clinical trial using an investigational product or device during the 30 days preceding recruitment Any physical or psychological disability that would impact study participation, such as severe cerebrovascular disease (ie. hemiparesis, cerebellar ataxia, etc.) or dementia Serum iPTH > 250 pmol/L within 30 days prior to screening visit Dysrhythmia or severe cardiac disease: CHF Class III-IV; unstable cardiovascular diagnosis (for example MI, CABG, PTCA, CVA, and TIA) within 90 days prior to recruitment Severe peripheral vascular disease Severe hyperkalemia (>6.5 mmol/L) consistently for the last 2 weeks Current active cancer (excluding basal cell carcinoma of the skin) Poorly controlled hypertension (systolic > 180mmHg or diastolic > 100mmHg) within 4 weeks prior to recruitment Anticipated live donor kidney transplant or any other planned major surgery over the study duration History of poor adherence to hemodialysis or medical regimen Any disease or condition, physical or psychological that, in the opinion of the investigator, would compromise the safety of the subject or the likelihood of achieving reliable results or increase the likelihood of the subject being withdrawn

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Aerobic Exercise program<br>Intervention of aerobic exercise | Behavioral: Aerobic Exercise program<br>* The 16-week program will consist of aerobic-type steady-state or interval exercises using a pedals attachable to the dialysis chairs. The purpose will be to slowly increase exercise duration by 5 minute increments to reach the goal of 30 min/treatment. The exercise program during hemodialysis sessions will contain a combination of aerobic and flexibility exercises, about 30 minutes of cycling with 10 minutes of warm up/stretching exercises and 10-15 minutes cool down. The frequency of exercise will be three sessions a week, during the first hour of dialysis treatment for the duration of 16 weeks. Blood pressure and heart continuous monitoring will be carried out during the exercise program. Exercise log sheets will be filled for each session for the 16 weeks.<br>|
| Other: Control<br>no aerobic exercise program | Other: Control<br>* No aerobic exercise is offered but baseline and end of study testing of the outcomes occur<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Gait speed | The gait speed will be measured with a timer (in seconds) as the subject will be asked to walk a 10 foot or 3 meter course and back as quickly as possible. Two readings will be taken and the average will be recorded. | at 24 weeks and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Pulse wave velocity (PWV) | PWV measurements will be performed between the carotid and femoral artery sites, to primarily measure the stiffness of the aorta. A 3-lead ECG will be used in conjunction with a tonometer to measure the pressure pulse waveform sequentially in the two peripheral artery sites | at 24 weeks and 48 weeks | 
| Change from Baseline Pulse wave analysis | Wave Reflections and Arterial Stiffness. Analysis of the systolic part of the central pressure waveform will be performed to evaluate PWV and the LV afterload. The main indices that were described above (in hemodynamic measurements) will be obtained by aortic PWA. | at 24 and 48 weeks | 
| Change from baseline Rand survey | RAND 36-item survey will be used to assess physical functioning and fatigue. This survey has been validated in the Hemodialysis population. The survey consists of 36 items and takes approximately 5-10 minutes to complete. | at 24 weeks and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, hemodialysis, pulse wave velocity, micro RNAs