Exercise in Obese Diabetic Patients With Chronic Kidney Disease (EX-ODCKD)

Structured Exercise in Obese Diabetic Patients With Chronic Kidney Disease

Patients with type 2 diabetes, obesity, and chronic kidney disease are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. This study seeks to determine if a structured exercise program will benefit the heart (improved exercise tolerance, decreased blood pressure) and/or the kidney (decreased protein loss in urine and stabilization of kidney function) and lead to improvements in diabetes, body composition, and quality of life.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Other: Exercise

Detailed Description

Patients with type 2 diabetes, obesity, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. However, there have been no randomized controlled trials to determine the benefits of exercise training in this population. This study seeks to substantiate the hypothesis that increasing energy expenditure by exercise training in the obese diabetic patient with CKD will result in the following benefits:

1. Renal benefits, including reduction in proteinuria and stabilization of glomerular filtration rate (GFR)
2. Cardiovascular benefits, including decreased blood pressure, decreased heart rate, and increased exercise tolerance.
3. Improved glucose control (lower glycated hemoglobin), lipid control (decreased cholesterol with improved atherogenic profile)
4. Improved body composition (weight loss, increased lean body mass and decreased fat mass).
5. Decreased inflammation (assessed by high-sensitivity C-reactive protein), endothelial dysfunction (assessed by flow-mediated dilatation), and oxidative stress (assessed by reduced glutathione).
6. Increased health-related quality of life.

In preparation for this proposal, the investigators performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (BMI > 30 kg/m2), and stage 2-4 CKD (eGFR 15-90 mL/min/1.73m2) with persistent proteinuria of > 200 mg/g. Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria. Exercise training resulted in a significant improvement in exercise duration during stress testing which persisted until 24 weeks. This was accompanied by significant decreases in resting systolic blood pressure and 24-hour proteinuria at 24 weeks. No changes were seen in the control group. The investigators concluded that exercise training in obese diabetic patients with CKD is feasible and results in a demonstrable training effect (increased exercise duration and decreased resting blood pressure). Moreover, it may decrease proteinuria and thus have a renoprotective effect.

The investigators now propose a larger-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD. This will be a 52-week randomized study based on the investigators' pilot study design with some modifications. As opposed to the 6-week training period and 18-week home exercise period utilized in the pilot study, subjects randomized to exercise will undergo 12 weeks of intensive exercise training in the exercise laboratory followed by 40 weeks of supervised home exercise training (total duration of study 1 year). Moreover, due to recent recommendations that resistance training be incorporated into exercise training regimens in type 2 diabetic patients, the investigators will incorporate resistance (strength) training in this proposal. The primary outcome variable will be change in proteinuria at 12 and 52 weeks. Secondary outcome variables will be change in albuminuria and estimated glomerular filtration rate (eGFR) at 12 and 52 weeks. In addition, the investigators will measure blood pressure (BP), glycated hemoglobin, lipid profile, C-reactive protein (CRP) levels, body weight and composition, endothelial dysfunction (by flow-mediated dilatation), and Quality of Life (QoL) evaluations. The Index of Coexistent Diseases (ICED) to measure comorbidities to determine if comorbid conditions had any influence on the outcomes of the study. The Center for Epidemiologic Studies Depression Scale (CES-D) will also be used to determine the influence of depression (covariate) on study outcomes and adherence with the study objectives.

This study will directly address the effects of a structured exercise program in a patient population at high risk for cardiovascular complications. The investigators will specifically address the novel idea that exercise will not only improve cardiovascular fitness but will also ameliorate the renal complications resulting from diabetes.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Hines, Illinois, United States, 60141-5000
      • Edward Hines Jr. VA Hospital, Hines, IL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diabetes mellitus
• CKD Stages 2-4
• BMI > 30
• Persistent proteinuria (urine protein/creatinine > 200 mg/g for > 3 mo)
• On treatment with ACE inhibitor or ARB
• On treatment with aspirin
• On treatment with statin (if LDL > 100)

Exclusion Criteria:

• Symptomatic neuropathy/retinopathy
• Positive stress test due to coronary arterial disease
• Symptomatic cardiovascular disease
• Congestive heart failure (New York Heart Association Class III or IV)
• Chronic obstructive pulmonary disease (FEV1 < 50% predicted and/or requires supplemental oxygen support during exercise)
• Complaints of angina during the stress test
• Cerebrovascular disease/cognitive impairment
• Renal transplant
• Inability to walk on the treadmill
• Any unforeseen illness or disability that would preclude exercise testing or training
• Participation in a formal exercise program within the previous 12 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Control group
Experimental: Exercise; Exercise Group	Other: Exercise; Exercise training for 12 weeks followed by home exercise for 40 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Proteinuria	12 weeks minus baseline
Change in Proteinuria	52 weeks minus baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Albuminuria	12 weeks minus baseline
Change in Albuminuria	52 weeks minus baseline
Change in Estimated Glomerular Filtration Rate (eGFR)	12 weeks minus baseline
Change in Estimated Glomerular Filtration Rate (eGFR)	52 weeks minus baseline

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Eileen G. Collins, PhD RN, Edward Hines Jr. VA Hospital, Hines, IL; Principal Investigator: David J Leehey, Edward Hines Jr. VA Hospital, Hines, IL

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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 17, 2009
• First Posted (Estimate): December 21, 2009

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: F7264-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No