Oxidative Stress in Chronic Kidney Disease: Diet and Exercise

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).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Other: caloric restriction; Other: aerobic exercise

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Springfield, Massachusetts, United States, 01109-3797
      • Springfield College
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Kidney Research Institute
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: caloric restriction; 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; 10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration
ACTIVE_COMPARATOR: aerobic exercise; supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration	Other: aerobic exercise; supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration
ACTIVE_COMPARATOR: caloric restriction and aerobic exercise; 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; 10 to 15% reduction in total daily calories (300 to 500 kcal reduction) from the usual daily energy consumption for 4 months duration; Other: aerobic exercise; supervised physical activity for a maximum of 30-45 minutes, 3 times per week for 4 months duration
NO_INTERVENTION: usual diet and usual activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: University of Washington

Publications and helpful links

General Publications

• Conley MM, McFarlane CM, Johnson DW, Kelly JT, Campbell KL, MacLaughlin HL. Interventions for weight loss in people with chronic kidney disease who are overweight or obese. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD013119. doi: 10.1002/14651858.CD013119.pub2.
• Jaramillo-Morales J, Korucu B, Pike MM, Lipworth L, Stewart T, Headley SAE, Germain M, Begue G, Roshanravan B, Tuttle KR, Himmelfarb J, Robinson-Cohen C, Ikizler TA, Gamboa JL. Effects of caloric restriction and aerobic exercise on circulating cell-free mitochondrial DNA in patients with moderate to severe chronic kidney disease. Am J Physiol Renal Physiol. 2022 Jan 1;322(1):F68-F75. doi: 10.1152/ajprenal.00270.2021. Epub 2021 Nov 29.
• Aydemir N, Pike MM, Alsouqi A, Headley SAE, Tuttle K, Evans EE, Milch CM, Moody KA, Germain M, Lipworth L, Himmelfarb J, Ikizler TA, Robinson-Cohen C. Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease. Nutr Metab Cardiovasc Dis. 2020 Jul 24;30(8):1375-1381. doi: 10.1016/j.numecd.2020.04.012. Epub 2020 Apr 21.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (ESTIMATE): June 28, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 100716