Exercise and Vascular Function in Chronic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the effects of 12 weeks of aerobic exercise training on blood vessel function in Stages 1-4 Chronic Kidney Disease.

Detailed Description
-----------------
The endothelium lines the inside of the blood vessels. A healthy endothelial lining acts as a defense mechanism against vascular injury, mediating vascular tone, vascular structure, and blood-vessel wall relations. Endothelial dysfunction marks the occurrence of cardiovascular injuries and is a critical step in the development of cardiovascular disease. Individuals with Chronic Kidney Disease (CKD) have an increased risk of cardiovascular disease and this may be related to poor blood vessel function. Interventions to improve blood vessel function in CKD are needed. Exercise training has been shown to improve blood vessel function in older subjects and those with heart disease but this has not been investigated in CKD. The National Kidney Foundation recommends exercise for dialysis patients to reduce cardiovascular risk however there is very little data regarding the benefits of exercise in earlier stages of CKD. The purpose of this study is to determine the effect of 12 weeks of exercise training on blood vessel function in moderate to severe CKD.

Official Title
-----------------
Exercise and Vascular Function in Chronic Kidney Disease

Conditions
-----------------
Chronic Renal Insufficiency

Intervention / Treatment
-----------------
* Other: Aerobic Exercise Training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: CKD Exercise and CKD Control Arms: Stage 1 - 4 Chronic Kidney Disease (eGFR 15 - 90 ml/min/1.73m2) Healthy Control Arm: eGFR > 90 ml/min/1.73m2) Exclusion Criteria: History of cardiovascular disease Uncontrolled hypertension Lung disease Liver disease Cancer Immunosuppressant or antiretroviral therapy Current tobacco use Pregnancy Hormone replacement therapy Unable to give consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD Aerobic Exercise Training<br>Chronic Kidney Disease participants randomly allocated to the CKD Exercise arm will receive 12 weeks of Aerobic Exercise Training three times per week. | Other: Aerobic Exercise Training<br>* Supervised outpatient moderate to vigorous aerobic training at 60% - 85% heart rate reserve, carried out for 45 minutes, three times per week over a twelve week period.<br>|
| No Intervention: CKD Control<br>Chronic Kidney Disease participants allocated to the the CKD Control arm will receive their standard routine care over a 12 week period. | |
| No Intervention: Healthy Control<br>Healthy participants will act as comparators, they will undergo baseline testing only and will not receive an intervention. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | Conduit artery endothelial function assessed by brachial artery flow mediated dilation; Microvascular endothelial function assessed by cutaneous vasodilation in response to local heating measured by microdialysis and laser Doppler flowmetry. | Change from baseline at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular function | Nitric oxide contribution to cutaneous microvascular vasodilation in response to local heating assessed by microdialysis and laser Doppler flowmetry | Change from baseline at 12 weeks | 
| Oxidative stress contribution to vascular dysfunction | Oxidative stress contribution to cutaneous vasodilation dysfunction in response to local heating assessed by microdialysis and laser Doppler flowmetry. | Change from baseline at 12 weeks | 
| Endothelial cell oxidative stress | Endothelial cell nitrotyrosine, NADPH oxidase, MnSOD oxidase content obtained from antecubital vein endothelial cells and assessed by fluorescence microscopy. | Changes from baseline at 12 weeks | 
| Plasma Oxidized Low Density Lipoprotein | Plasma oxidized low density lipoprotein measured by ELISA | Change from baseline at 12 weeks | 
| F2-isoprostanes | Urinary F2-isoprostanes measured by ELISA | Change from baseline at 12 weeks | 
| Pulse Wave Analysis | Central blood pressure and augmentation index assessed by oscillometry and radial tonometry | Change from baseline at 12 weeks | 
| Arterial Stiffness | Carotid to femoral pulse wave velocity and assessed by tonometry | Change from baseline at 12 weeks | 
| Ambulatory Blood Pressure | 24 hour blood pressure recorded by oscillometric monitors | Change from baseline at 12 weeks | 
| Peak Aerobic Capacity | Peak oxygen uptake (VO2peak/max) during incremental cycling exercise until exhaustion | Change from baseline at 12 weeks | 
| Physical Function | Dexterity by the '9-Hole Peg Test'; Endurance by the '2 Minute Walk Endurance Test'; locomotion by the '4 Meter Gait Speed Test'; isometric handgrip strength test by handgrip dynamometry. | Change from baseline at 12 weeks | 
| Habitual Physical Activity | Daily average energy expenditure, step count and physical activity intensity level by accelerometry. | Change from baseline at 12 weeks | 
| Knee Extensor Strength | Maximal isometric knee extensor strength | Change from baseline at 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise Therapy, Endothelium, vascular, Blood Vessels