Peripheral Vasodilation in Obese Humans
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Change in limb blood flow in response to barium chloride infusion which inhibits potassium channel vasodilation.
研究概览
简要总结
The growing population of obese adults is predicted to create a large public health burden in the next few decades. This study examines function of small blood vessels providing blood flow to skeletal muscles, to test if younger obese individuals (≤40 years old, BMI >30) are already displaying reductions in blood vessel function. This study will test if the signals blood vessels use to increase blood flow are changing in these same subjects. Findings from this study may help create treatments to delay or prevent some of the negative effects of obesity on vascular health.
详细描述
This study initially started in June 2011(IND 122211). The original Aim 1 was completed and showed lean and obese groups did not differ in endothelial dependent dilation (EDD) and exercise dilation responses. The original Aim 2 was contingent upon there being a difference between lean and obese groups in Aim 1 and therefore was not pursued.
The investigators now plan to continue this study by assessing 2 additional aims that are consistent with the original purpose of the study and are discussed below:
The growing population of obese adults is predicted to create a large public health burden in the next few decades. Obese humans also exhibit reduced exercise capacity and lower muscle blood flow. The overall goal of this research program is to investigate the obesity-related changes in microvascular function contributing to impaired muscle blood flow. This proposal seeks to directly test vascular control in human skeletal muscle resistance arteries in exercising humans. The investigators propose to study younger obese adults, without confounding effects of age, metabolic syndrome, or diabetes-before the negative effects of obesity can exert their full negative impact. The general hypothesis is that endothelium dependent dilation (EDD) and functional (exercise) vasodilation is impaired via shift away from nitric oxide bioavailability and a shift toward increased reliance on potassium (K+) mediated vasodilation.
Primary objective To determine whether role of K+ mediated vasodilation differs between lean and obese adults.
Aims Aim 1: To test the hypothesis that obesity induces an endothelial phenotype change that creates an environment for both EDD and exercise dysfunction. The investigators propose that obesity alters endothelial enzymes, which help explain the mechanistic changes in vasodilation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: ≥18 - ≤ 40 years of age
- •Blood pressure systolic ≤125 and diastolic ≤85 mmHg (Lean control) and <140 and diastolic <90 mmHg (Obese subjects)
- •BMI <25 kg/m2 (Lean control) and ≥30 kg/m2 (Obese subjects)
- •Fasting blood glucose <100 mg/dL
- •Fasting LDL <130 mg/dL
- •Fasting blood triglycerides <150 mg/dL
- •Females: Premenopausal with a regular menstrual cycle. Negative pregnancy test. Note: Must be studied in the early follicular phase (day 1-5) of their menstrual cycle or the low hormone phase of oral contraceptive use.
排除标准
- •Specific to obese subjects only (to exclude obese subjects with metabolic syndrome):
- •a. If Systolic BP 130 ≤ BP < 140 mmHg or Diastolic BP 85 ≤ BP < 90 mmHg i. HDL < 40 mg/dL for men ii. HDL < 50 mg/dL for women
- •Increased risk of bleeding
- •Sensitivity to lidocaine
- •Procoagulant or other clotting disorders
- •Taking cardiovascular medications (anti-hypertensives, statins, platelet inhibitors, etc.) or metabolic medications (insulin-sensitizing)
- •Regularly (≥5 days/week) take acetylsalicylic acid and/or non-steroidal anti-inflammatory drugs (NSAIDs)
- •Self-reported current diagnosis of exhibiting obstructive sleep apnea
- •Self-reported current or past diagnosis of diabetes
- •Self-reported history of peripheral vascular disease
- •Self-reported history of hepatic disease
- •Self-reported history of renal disease
- •Self-reported history of hematologic disease
- •Self-reported history of stroke
- •Current use of tobacco (i.e. smoke, smokeless, and vapor). Prior tobacco use with >1 year abstaining is allowed.
- •Participation in vigorous aerobic exercise >90 minutes per week
- •Arterial structures in the arm that are not conducive to study in the laboratory setting
- •Females: Self-reported pregnancy and/or breastfeeding, diagnosed with polycystic ovarian syndrome, or without regular menses. Urine pregnancy test will be performed on study day to ensure subject is not pregnant on study day.
- •An abnormality or contraindication to study participation which is not covered in the eligibility criteria.
研究组 & 干预措施
EDD Obese
On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible obese subjects will undergo Drug Trial 1 (EDD) (described in Intervention section).
干预措施: Drug Trial 1 (EDD) (Drug)
EDD Lean
On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible lean subjects will undergo Drug Trial 1 (EDD) (described in Intervention section).
干预措施: Drug Trial 1 (EDD) (Drug)
ROV Obese
On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible obese subjects will undergo Drug Trial 2 (ROV) (described in Intervention section).
干预措施: Drug Trial 2 (ROV) (Drug)
ROV Lean
On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible lean subjects will undergo Drug Trial 2 (ROV) (described in Intervention section).
干预措施: Drug Trial 2 (ROV) (Drug)
结局指标
主要结局
Change in limb blood flow in response to barium chloride infusion which inhibits potassium channel vasodilation.
时间窗: Through study completion
Change in limb blood flow (ml/min), measured with Doppler ultrasound, in response to barium chloride infusion (inhibition of K+ vasodilation). This will be calculated by taking the difference between the stimulus blood flow response and the stimulus blood flow response in the presence of barium chloride. These changes will be compared between lean and obese.
Change in limb blood flow in response to stimuli that cause vasodilation (ATP, ISO, BK, Ach, muscle contractions).
时间窗: Through study completion
Change in limb blood flow (ml/min), measured with Doppler ultrasound, in response potassium vasodilation (EDD or ROV). The change in blood flow will be calculated by taking the difference between the stimulus blood flow response and the baseline blood flow. These changes will be compared between lean and obese.
次要结局
- Change in blood flow in response to L-NMMA and ketorolac in the presence of barium chloride(Minutes/seconds between baseline and peak response to stimuli)
- Endothelial cell collection from arterial catheter to measure protein expression.(Through study completion)