Sympatholysis in Chronic Kidney Disease
- Conditions
- Chronic Kidney Disease
- Interventions
- Drug: PlaceboBehavioral: Exercise TrainingBehavioral: Control to Exercise (Stretching)
- Registration Number
- NCT02411773
- Lead Sponsor
- Emory University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
- 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
- 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
- Low blood pressure with BP less than 100/50 mmHg
- Pregnancy or plans to become pregnant
- Current treatment with monoamine oxidase inhibitors (MAOIs)
- Inability to exercise on a stationary bicycle
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Exercise Training plus Sodium Bicarbonate 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. Exercise Training plus Sodium Bicarbonate Exercise Training 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. Exercise Training plus Placebo 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. Exercise Training plus Placebo Exercise Training 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. Control to Exercise (Stretching) plus Sodium Bicarbonate 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. Control to Exercise (Stretching) plus Sodium Bicarbonate Control to Exercise (Stretching) 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. Control to Exercise (Stretching) plus Placebo 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. Control to Exercise (Stretching) plus Placebo Control to Exercise (Stretching) 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.
- Primary Outcome Measures
Name Time Method Change in muscle oxygenation after exercise/stretching training 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 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 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 Outcome Measures
Name Time Method Change in Functional Sympatholysis Baseline, 30 minutes Functional sympatholysis is determined by measuring the change in forearm oxygenation via near infrared spectroscopy (NIRS), and forearm blood flow and conductance using ultrasound, during sympathetic activation induced by lower body negative pressure (LBNP), at rest and during handgrip exercise. NIRS measures and records tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Change in muscle interstitial pH after handgrip exercise Baseline, 30 minutes 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 Phenylephrine Baseline, 30 minutes Vascular function is measured as venoconstriction after administration of phenylephrine. 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.
Trial Locations
- Locations (1)
Atlanta VA Medical Center
🇺🇸Decatur, Georgia, United States