Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 6
- 主要终点
- Change in functional sympatholysis
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 to explore what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate). This study will also test whether or not regular exercise on a bicycle and/or treatment with 6R-BH4 (Kuvan) pills, or histidine and beta-alanine supplementation improves these measures during exercise. 6R-BH4 is currently FDA-approved for use in patients with certain forms of a disease called phenylketonuria, but it is not currently FDA approved for blood pressure or exercise capacity in people with CKD.
详细描述
The major problem addressed in this study is to understand mechanisms underlying poor exercise capacity in patients with chronic kidney disease (CKD). Prior research has found that CKD patients have an exaggerated increase in blood pressure during certain forms of exercise that could contribute to exercise dysfunction as well as cardiovascular disease. This study will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of simple measures such as exercise training on a stationary bicycle, and treatment with 6R-BH4, a drug that is currently FDA-approved for the treatment of phenylketonuria, but has been shown to have beneficial effects on vascular health in patients with kidney disease. This study will also examine the effects of exercise with histidine and beta-alanine supplementation. Histidine and beta-alanine are two over-the-counter supplements commonly used to enhance sports performance in athletes.
Prior to the intervention portion of this study, the researchers will measure how much the vein constricts in response to adrenaline in CKD patients versus controls. The study will also measure muscle pH, and muscle oxygenation during exercise in CKD patients and controls.
The intervention portion of the study will test whether aerobic exercise training with and without 6R-BH4, or with and without histidine and beta-alanine supplementation might help muscle pH and adrenaline levels, vascular reactivity, muscle oxygenation, and the exaggerated blood pressure response during exercise in CKD patients. Participants will be randomized using a 2x2 factorial design to exercise training (ET) with 6R-BH4, ET with placebo, stretching (control condition to exercise) with 6R-BH4, and stretching with placebo. Participants will undergo exercise training on a stationary bicycle, or stretching exercises, 3 times per week for 6-14 weeks (depending on availability of the participant).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Supportive Care
- 盲法
- Single (Participant)
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
- 否
入选标准
- •for Chronic Kidney Disease Patients:
- •Stage III or IV Chronic Kidney Disease, defined as reduction in estimated glomerular filtration rate (eGFR) to 15-59 cc/minute as calculated by the modified Modification of Diet in Renal Disease (MDRD) Study equation or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
- •Stable renal function, with no greater than a 30% reduction in eGFR over the prior 3 months
- •Does not exercise regularly (defined as exercising less than 20 minutes twice per week)
- •Willing and able to cooperate with the study protocol
- •Inclusion Criteria for Control Study Participants:
- •Does not exercise regularly (defined as exercising less than 20 minutes twice per week)
- •Willing and able to cooperate with the study protocol
排除标准
- •severe CKD (eGFR<15 cc/minute)
- •ongoing drug or alcohol abuse
- •diabetic neuropathy
- •any serious systemic disease that might influence survival
- •severe anemia with hgb level <9 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 BP greater than 170/100 mm Hg
- •low blood pressure with BP less than 100/50
- •pregnancy or plans to become pregnant
- •current treatment with monoamine oxidase (MAO) inhibitors
- •inability to exercise on a stationary bicycle
研究组 & 干预措施
Stretching + 6R-BH4
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: 6R-BH4 (Drug)
Exercise training + 6R-BH4 placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the study drug 6R-BH4.
干预措施: Folic acid (Dietary Supplement)
Exercise training + 6R-BH4 placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the study drug 6R-BH4.
干预措施: 6R-BH4 placebo (Other)
Stretching + 6R-BH4
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: Folic acid (Dietary Supplement)
Stretching + 6R-BH4
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: Stretching (Other)
Stretching + placebo
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo instead of the active study drug.
干预措施: 6R-BH4 placebo (Other)
Stretching + placebo
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo instead of the active study drug.
干预措施: Folic acid (Dietary Supplement)
Stretching + placebo
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo instead of the active study drug.
干预措施: Stretching (Other)
Exercise training + histidine and beta-alanine
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take histidine and beta-alanine supplementation.
干预措施: Exercise training (Other)
Exercise training + histidine and beta-alanine
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take histidine and beta-alanine supplementation.
干预措施: Histidine and beta-alanine supplementation (Dietary Supplement)
Exercise training + histidine and beta-alanine placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the histidine and beta-alanine supplementation.
干预措施: Exercise training (Other)
Exercise training + 6R-BH4
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: 6R-BH4 (Drug)
Exercise training + 6R-BH4
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: Folic acid (Dietary Supplement)
Exercise training + 6R-BH4
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take the study drug 6R-BH4.
干预措施: Exercise training (Other)
Exercise training + 6R-BH4 placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the study drug 6R-BH4.
干预措施: Exercise training (Other)
Exercise training + histidine and beta-alanine placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. This arm will also take a placebo to match the histidine and beta-alanine supplementation.
干预措施: Histidine and beta-alanine placebo (Other)
结局指标
主要结局
Change in functional sympatholysis
时间窗: Baseline, Week 12
Muscle oxygenation during exercise and sympathoexcitation will be measured.
Change in exaggerated pressor responses during exercise
时间窗: Baseline, Week 12
Blood pressure and sympathetic responses during exercise will be measured.
Change in vascular alpha 1 adrenergic responsiveness
时间窗: Baseline, Week 12
Changes in vascular diameter in response to phenylephrine will be measured.
次要结局
- Renal artery resistance during exercise(Baseline, Week 12)
- Change in endothelial function(Baseline, Week 12)
- Change in vascular stiffness(Baseline, Week 12)
研究者
Jeanie Park
Associate Professor
Emory University