Free Fatty Acids-Induced Hypertension, Endothelial Dysfunction, Inflammation, Insulin Resistance, and Autonomic Dysfunction in Lean and Obese Subjects (Aim #2)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Change in Flow-mediated Dilation
研究概览
简要总结
The purpose of this study is to see if salsalate, an Nuclear factor-kappaB (NF-κB) mediated inflammation inhibitor, or carvedilol, an α- and β-blocker, will protect against free fatty acid induced hypertension, insulin resistance, endothelial dysfunction, inflammation and oxidative stress, and autonomic dysfunction in obese normotensive subjects.
详细描述
During postprandial lipemia, dietary triglycerides transported by intestinal chylomicrons are hydrolyzed by lipoprotein lipase lining the vascular bed, with subsequent release of FFA for transport across the endothelium. Whether the intermittent flux of FFA has the same impact as the i.v. lipid infusion will be examined. Decreased endothelial function has been reported after a single or long-term dietary high fat load in normal subjects; however, others have found no effects on brachial artery vasoreactivity. Our preliminary studies indicate that high oral fat loads (60 g) resulted in higher FFA levels and BP changes, and reduced FMD compared to low fat load (25 g).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females
- •Obese subjects (body mass index (BMI) ≥ 30 kg/m^2)
- •18 and 65 years
- •Blood pressure reading < 140/80 mm Hg and no prior history of hypertension
排除标准
- •History of diabetes mellitus
- •History of hypertension
- •Fasting triglyceride levels > 250 mg/dL
- •Liver disease (ALT 2.5x > upper limit of normal)
- •Serum creatinine ≥1.5 mg/dL
- •Smokers, drug or alcohol abuse
- •Mental condition rendering the subject unable to understand the scope and possible consequences of the study
- •Female subjects who are pregnant or breast feeding
研究组 & 干预措施
Salsalate
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Salsalate (Drug)
Salsalate
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Intralipid 20% (Drug)
Carvedilol
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Carvedilol (Drug)
Carvedilol
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject has no side effects, the dose will be increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Intralipid 20% (Drug)
Placebo
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose will be increased to two placebo tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Placebo (Drug)
Placebo
Obese, normotensive, healthy subjects will receive an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose will be increased to two placebo tablets twice daily for the remaining four weeks. The subjects will then receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
干预措施: Intralipid 20% (Drug)
结局指标
主要结局
Change in Flow-mediated Dilation
时间窗: Pre-dose (Week 6), within 24 hours at Week 6 visit
The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion
Change in Systolic Blood Pressure.
时间窗: Pre-dose (Baseline), within 4 hours at Baseline visit
Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion.
Change in Systolic Blood Pressure
时间窗: Pre-dose (Week 6), within 24 hours at Week 6 visit
Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion.
次要结局
- Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6)(Baseline, 6 weeks)
- Change in Pulse Wave Velocity (PWV)(Baseline, 6 weeks)
- Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks(Baseline, 6 weeks)
- Change in Augmentation Index (AIx)(Baseline, 6 weeks)
- Change in Diastolic Blood Pressure From Baseline to 6 Weeks(Baseline, 6 weeks)
- Change in Oxidative Stress Markers.(Baseline, 6 weeks)
- Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP)(Baseline, 6 weeks)
研究者
Guillermo Umpierrez, MD
Professor
Emory University