The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 2
- 主要终点
- Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
研究概览
简要总结
Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise
- •CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
- •willing and able to cooperate with the protocol
- •CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
- •controls will be matched for age, gender, race, and hypertensive status.
排除标准
- •severe CKD (eGFR<30 cc/minute)
- •drug or alcohol abuse
- •any serious systemic disease that might influence survival
- •severe anemia with hgb level <10 g/dL
- •clinical evidence of congestive heart failure or ejection fraction below 35%
- •any history of past myocardial infarction or cerebrovascular accident
- •symptomatic heart disease determined by electrocardiogram, stress test, and/or history
- •treatment with central alpha agonists
- •uncontrolled hypertension with BP greater than 160/90 mm Hg
- •low blood pressure with BP less than 110/60
- •history of nephrolithiasis
- •pregnancy or plans to become pregnant
- •treatment with vitamin C within the past 3 months
- •hepatic enzyme concentrations greater than 2 times the upper limit of normal
- •HIV infection
- •surgery within the past 3 months
- •previous treatment with BH4
- •known hypersensitivity to BH4
- •any condition that places the participant at high risk of poor adherence or poor follow-up
- •patients must be willing to use an acceptable method of contraception if of childbearing age
研究组 & 干预措施
Tetrahydrobiopterin + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily
干预措施: Tetrahydrobiopterin (Drug)
Tetrahydrobiopterin + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily
干预措施: Folate (Dietary Supplement)
Placebo + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily
干预措施: Placebo (Drug)
Placebo + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily
干预措施: Folate (Dietary Supplement)
结局指标
主要结局
Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
时间窗: Baseline, 12 weeks
次要结局
- Change in Mean Central Augmentation Index (AIx)(Baseline, 12 weeks)
- Change in Heart-rate-corrected Augmentation Index (AIx)(Baseline, 12 weeks)
研究者
Jeanie Park
Assistant Professor of Medicine
Emory University