Oxidative Stress in Chronic Kidney Disease: Diet and Exercise

Study Overview
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Brief Summary
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The central aim of this study is to improve understanding of how metabolic pathways that contribute to adiposity also amplify risks of kidney disease progression and cardiovascular disease in subjects with moderate to severe CKD. In order to achieve this goal, we propose the following aims through a randomized 2x2 factorial design trial in subjects with moderate to severe CKD: (a) To assess the feasibility of implementing aerobic exercise and caloric restriction interventions, and (b) To examine the effects of aerobic exercise and caloric restriction on a metabolic risk profile, including systemic measures of oxidative stress, inflammation, insulin resistance, and endothelial dysfunction. Hypothesis: We hypothesize that implementation of caloric restriction and aerobic exercise is feasible and can improve the metabolic milieu (as assessed by measures of oxidative stress, inflammation, insulin resistance, and endothelial dysfunction) in subjects with moderate to severe CKD. Interim analysis may be performed (no specific plan at this time).

Official Title
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Oxidative Stress in Chronic Kidney Disease: Diet and Exercise

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Other: caloric restriction
* Other: aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III-IV CKD measured by the MDRD equation with eGFR 15-60 ml/min/1.73m2; Age 18-75 years; BMI ≥ 25; Life expectancy ≥ 1 year; Ability to understand and provide informed consent. Exclusion Criteria: Any acute inflammatory condition (including chronic infection requiring treatment, and collagen vascular disease including active gout); Pregnancy; Taking high-dose anti-oxidants (Vitamin E or C); Chronic use of anti-inflammatory medication except low dose (< 10mg/d) prednisone and aspirin (< 100 mg/day); Significant cardiac or vascular disease (symptomatic disease or CV event including congestive heart failure within 6 months); Significant occlusive atherosclerotic disease or ischemic disease (on non-invasive or invasive diagnostic procedures); Significant physical immobility or disabilities (joint replacement, muscular disorders); Type I diabetes mellitus, or Type II requiring insulin therapy; History of poor adherence to medical regimen; Those subjects who have a diagnosis of atrial fibrillation or a pacemaker will be allowed in the study but will not undergo Arterial Tonometry (PWV) studies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: caloric restriction<br>10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration | Other: caloric restriction<br>* 10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration<br>|
| Active Comparator: aerobic exercise<br>supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration | Other: aerobic exercise<br>* supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration<br>|
| Active Comparator: caloric restriction and aerobic exercise<br>10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration, and supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration | Other: caloric restriction<br>* 10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration<br>Other: aerobic exercise<br>* supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration<br>|
| No Intervention: usual diet and usual activity<br>usual diet and usual activity | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a change in plasma F-2-isoprostane concentration |  | baseline and 4 months | 
| a change in VO2 max |  | baseline and 4 months | 
| a change in weight |  | baseline and 4 months | 
| a change in absolute fat mass |  | baseline and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a change in biomarkers of inflammation |  | baseline and 4 months | 
| a change in biomarkers of endothelial dysfunction |  | baseline and 4 months | 
| a change in biomarkers of insulin resistance |  | baseline and 4 months |