Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease
Overview
- Phase
- Phase 1
- Intervention
- Sodium Bicarbonate
- Conditions
- Chronic Kidney Disease
- Sponsor
- Emory University
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Change in muscle oxygenation after exercise/stretching training
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to find out why patients with chronic kidney disease (CKD) have poor exercise capacity and what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate).
Detailed Description
Patients with chronic kidney disease (CKD) suffer from exercise intolerance and poor physical capacity which contributes to increased cardiovascular risk in this patient population. Prior studies have shown that CKD patients have an exaggerated increase in blood pressure (BP) during both static and rhythmic exercise. Such abnormal hemodynamic responses to exercise can contribute to poor physical capacity and abnormal muscle blood flow during exercise in these patients. The goals of this project are to investigate the mechanisms and potential therapies targeting the abnormal hemodynamic response during exercise in CKD by examining the roles of impaired vasodilation, and exaggerated vasoconstriction.
Investigators
Jeanie Park
Associate Professor
Emory University
Eligibility Criteria
Inclusion Criteria
- •Veterans with Stages III and IV Chronic Kidney Disease (CKD)
- •Kidney transplant recipients with varying degrees of kidney function
- •Veterans 18-75 years old, without kidney disease, as study controls
- •Exercise less than 20 minutes twice per week
- •Willing and able to cooperate with the protocol
Exclusion Criteria
- •Severe CKD (estimated glomerular filtration rate (eGFR) \< 15 cc/minute)
- •Metabolic alkalosis (serum bicarbonate \> 28 meq/L)
- •Ongoing drug or alcohol abuse
- •Diabetic neuropathy
- •Any serious systemic disease that might influence survival
- •Severe anemia with hemoglobin (Hbg) level \< 10 g/dL
- •Clinical evidence of congestive heart failure or ejection fraction below 35%
- •Symptomatic heart disease determined by prior electrocardiogram, stress test, and/or history
- •Treatment with central alpha agonists (clonidine)
- •Uncontrolled hypertension with blood pressure (BP) greater than 170/100 mmHg
Arms & Interventions
Exercise Training plus Sodium Bicarbonate
Subjects with CKD will undergo exercise training on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each exercise session three times a week.
Intervention: Sodium Bicarbonate
Exercise Training plus Sodium Bicarbonate
Subjects with CKD will undergo exercise training on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each exercise session three times a week.
Intervention: Exercise Training
Exercise Training plus Placebo
Subjects with CKD will undergo exercise training on a stationary bicycle,for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Intervention: Placebo
Exercise Training plus Placebo
Subjects with CKD will undergo exercise training on a stationary bicycle,for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Intervention: Exercise Training
Control to Exercise (Stretching) plus Sodium Bicarbonate
Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each stretching session three times a week.
Intervention: Sodium Bicarbonate
Control to Exercise (Stretching) plus Sodium Bicarbonate
Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each stretching session three times a week.
Intervention: Control to Exercise (Stretching)
Control to Exercise (Stretching) plus Placebo
Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Intervention: Placebo
Control to Exercise (Stretching) plus Placebo
Subjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Intervention: Control to Exercise (Stretching)
Outcomes
Primary Outcomes
Change in muscle oxygenation after exercise/stretching training
Time Frame: Baseline, Week 12
Near-infrared spectroscopy (NIRS) will measure and record tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Change in muscle interstitial pH after exercise/stretching training
Time Frame: Baseline, Week 12
Near-infrared spectroscopy (NIRS) will give an estimation of the pH levels within the muscle interstitial space. Muscle interstitial pH markedly decreases during exercise, and is often lower than blood pH with a larger intracellular to interstitial pH gradient. CKD patients may have less ability to buffer pH changes in the interstitial space during exercise. Bicarbonate supplementation may improve muscle interstitial buffering capacity during exercise, and prevent exaggerated reductions in muscle interstitial pH during exercise.
Change in venoconstriction after exercise/stretching training
Time Frame: Baseline, Week 12
Dorsal hand vein model will be used to assess vascular alpha-1 adrenergic responsiveness by measuring the degree of venous constriction in response to varying dosages of local phenylephrine (PE) infusion.
Secondary Outcomes
- Change in Functional Sympatholysis(Baseline, 30 minutes)
- Change in muscle interstitial pH after handgrip exercise(Baseline, 30 minutes)
- Change in Venoconstriction after Phenylephrine(Baseline, 30 minutes)