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临床试验/NCT03506646
NCT03506646已完成不适用

Dietary Nitrate Supplementation and Thermoregulation During Exercise

University of Nebraska2 个研究点 分布在 1 个国家目标入组 11 人开始时间: 2018年9月5日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
11
试验地点
2
主要终点
Brachial Artery Endothelial Function

研究概览

简要总结

This is a double-blinded, randomized, crossover design study to assess the effects of dietary nitrate supplementation (beetroot juice) on peripheral artery disease (PAD) patients (ages 50-85) diagnosed with Fontaine stage I or II PAD (as determined by vascular surgeon at UNMC). Exclusion criteria include: 1) experience severe claudication (leg pain) at rest or tissue loss due to PAD (Fontaine stage III and IV), 2) have limited walking capacity due to conditions other than PAD, 3) are already supplementing with a form of dietary nitrate, or 4) have an allergy to beetroot juice.

Subjects will be required to visit the lab 3 times and will be randomized to receive either the supplement or the placebo for the 2nd and 3rd visits. There will be a washout period of 14 days between the 2nd and 3rd visits. Visit 1 will take approximately 2 hours and the 2nd/3rd visits will take approximately 1.5 hours. Total experimentation period will last approximately 15 days.

Visit 1 will consist of non-invasive baseline testing including assessment of endothelial function (flow-mediated dilation by ultrasound imaging), maximal walking capacity (Gardner treadmill protocol), leg function (near-infrared spectroscopy, time to onset claudication, blood flow to lower extremities), and body core temperature (rectal thermometer). Visits 2 and 3 will require consumption of either the supplement or placebo. The same tests from the baseline measurements will be performed for visits 2 and 3. There will be a recommended fourth visit, albeit not required, to review study results.

详细描述

Background and rationale The vast majority of the research involving dietary nitrate supplementation, namely beetroot juice, has been performed mostly on samples of healthy populations. A few clinical populations have been studied, including heart failure with preserved ejection fraction, chronic obstructive pulmonary disease (COPD), and peripheral artery disease (PAD). In various populations, beetroot juice (BRJ) has been shown to decrease overall blood pressure, increase blood flow, increase muscle tissue oxygenation, improve body core temperature regulation, and increase exercise tolerance while decreasing the oxygen cost of exercise.

Blood pressure BRJ supplementation has been shown to have an immediate effect on reducing blood pressure, with the most substantial decreases recorded within approximately 2.5-3 hours following supplement consumption [1, 2]. Systolic, diastolic, and mean arterial blood pressures showed decreases of 10.4±3 mmHg, 8.1±2.1 mmHg, and 8.0±2.1 mmHg, respectively, in healthy volunteers [2]. During exercise in healthy individuals, systolic blood pressure remained lower throughout varying exercise intensities [1]. Blood pressure was also reduced in heart failure with preserved ejection fraction patients. After an acute dose of BRJ, resting systolic blood pressure significantly decreased when compared to placebo conditions (BRJ 127 ± 14 mmHg; placebo134 ± 14 mmHg) [3]. A slight reduction in systolic blood pressure during exercise may be beneficial to PAD patients. Hypertension, or high blood pressure, is a major risk factor for the development of PAD [4]. Decreasing overall blood pressure and slightly decreasing systolic blood pressure in response to light activity would result in a decrease in unnecessary stress placed on the cardiovascular system at rest and during exercise.

In a study involving PAD patients where 7 of the 8 participants were classified as either hypertensive or prehypertensive, BRJ consumption caused a significant reduction in diastolic blood pressure during rest that was maintained during exercise testing [5]. The study concludes that their data suggest that BRJ supplementation reduces blood pressure in PAD patients and this effect is maintained throughout exercise [5].

Oxygen delivery and muscle tissue oxygenation Oxygen demand of working muscle increases as activity level increases the efficiency of oxygen delivery and oxygen utilization is crucial to muscle function, as well as a necessary increase in blood flow. This is especially important in PAD patients; increasing oxygenation to areas of skeletal muscle ischemia may increase physical function. By using near-infrared spectroscopy, muscle tissue oxygenation can be examined. During cycling in healthy males supplementing with BRJ, the right vastus lateralis muscle oxyhemoglobin concentrations were greater than that of the placebo condition [6]. While cycling at a moderate intensity, the male cyclists had a 13% reduction in deoxyhemoglobin concentration amplitude post-supplementation, which indicated a reduction in fractional oxygen extraction in the right vastus lateralis muscle [6]. These results suggest that BRJ supplementation may promote a better balance between localized oxygen delivery and utilization as an index of muscle fractional oxygen extraction [6]. Overall, BRJ supplementation has been shown to increase working muscle tissue oxygenation during exercise.

In PAD patients, the oxygenation of the gastrocnemius with the worst PAD symptoms was monitored during a walking cardiopulmonary exercise test. Subjects showed a 48% reduction in deoxyhemoglobin concentration amplitude following BRJ supplementation, which indicated that fractional oxygen extraction was reduced [5]. During the exercise protocol, deoxyhemoglobin amplitude measures for the BRJ supplementation group at 100 and 200 seconds into exercise were reduced by 44% and 53%, respectively [5]. This response implies that BRJ supplementation in PAD patients improves a balance between local oxygen delivery and utilization as an index of muscle fractional oxygenation extraction by the working muscle. Increasing oxygenation to areas of skeletal muscle ischemia in PAD patients may increase physical function, but in order for this to be as efficient as possible, a dose-response relationship must be determined.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Double (Participant, Investigator)

入排标准

年龄范围
50 Years 至 85 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • be able to give written, informed consent
  • demonstrate positive history of chronic claudication
  • have a history of exercise-limiting claudication
  • have an ankle/brachial index < 0.90 at rest
  • have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.
  • be between 50-85 years old

排除标准

  • pain at rest (severe claudication) and/or tissue loss due to PAD (Fontaine stage III and IV)
  • acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
  • limited walking capacity due to other conditions other than PAD
  • a form of nitrate supplementation already included in their diet/regimen
  • an allergy to beetroot juice

结局指标

主要结局

Brachial Artery Endothelial Function

时间窗: Pre and post treatment

Endothelial function will be assessed using flow mediated dilation to measure vasodilation in the brachial artery (baFMD).

次要结局

  • Leg Endothelial Function(Pre and Post treatment)
  • Muscle Tissue Oxygenation(2 days)
  • Physical Walking Capacity(maximum of 14 minutes each day for 2 days)
  • Autonomic Nervous System Activity(maximum of 60 minutes each day for 2 days)
  • Microvascular Function(maximum of 30 minutes each day for 2 days)
  • Blood Nitrate/Nitrite Levels(2 days)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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