Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Change in muscle oxygenation after exercise/stretching training
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Sodium Bicarbonate (Drug)
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.
干预措施: Sodium Bicarbonate (Drug)
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.
干预措施: Exercise Training (Behavioral)
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.
干预措施: Placebo (Drug)
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.
干预措施: Exercise Training (Behavioral)
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.
干预措施: Control to Exercise (Stretching) (Behavioral)
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.
干预措施: Placebo (Drug)
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.
干预措施: Control to Exercise (Stretching) (Behavioral)
结局指标
主要结局
Change in muscle oxygenation after exercise/stretching training
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)
研究者
Jeanie Park
Associate Professor
Emory University