The Autonomic Nervous System and the Metabolic Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Insulin Resistance
研究概览
简要总结
The overall goal of this proposal is to determine the role of the autonomic nervous system in the insulin resistant state associated with obesity and the metabolic syndrome. Obesity results from an accumulation of excessive fat deposit due to increase caloric intake or decrease energy expenditure, this condition is usually associated with diseases such as hypertension or diabetes, a cluster known as the metabolic syndrome. The first step in the development of the metabolic syndrome is a resistance to the action of insulin. The mechanism underlying insulin resistance in obesity is still unknown, however some investigators have proposed that the autonomic nervous system, particularly the increase sympathetic activation in obesity may play an important role. We have extensive experience studying the role of the autonomic nervous system in the cardiovascular alterations associated with obesity by producing complete autonomic withdrawal with a drug named trimethaphan. We propose to use the same approach to study the role of the autonomic nervous system in the development of insulin resistance in obesity.
详细描述
The purpose of this study is to look at the role of the autonomic nervous system, an involuntary nervous system that controls your blood pressure, in insulin resistance and the metabolic syndrome. Insulin is a substance that helps your body use the sugar in the food that you eat. Some people's tissues stop reacting in a normal way to insulin, a condition known as insulin resistance. A person with insulin resistance can have other health problems, such as obesity, high cholesterol, and high blood pressure. These problems together are called the metabolic syndrome. We think that the autonomic or involuntary nervous system controls the way your body responds to insulin. This system is changed in obese people, and we think that it may cause the insulin resistance. We plan to study this with two drugs -trimethaphan and L-NMMA. Neither of these drugs are approved by the Food and Drug Administration (FDA), and they will be used for research purposes only.
Fifty people will take part in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For lean subjects:
- •21 subjects aged 18-60 yr.
- •All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities.
- •Body mass index < 25Kg/m^2 .
- •Female volunteers of childbearing potential will undergo HCG pregnancy test at screening and again on the study day.
- •For Obese subjects with metabolic syndrome:
- •21 subjects aged 18-60 yr.
- •All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities.
- •Body mass index > 30Kg/m^
- •Participants will be enrolled if they met at least three of the following criteria for metabolic syndrome (Expert panel, Jama 2001):
- •Waist circumference >102 cm in men and >88 cm in women
- •High fasting blood sugar (>110 mg%)
- •Triglyceride levels >150 mg%
- •Low HDL cholesterol (<40 mg% for men; <50 mg% for women)
- •High blood pressure (systolic=130 and diastolic = 85 mmHg) • Female volunteers of childbearing potential will undergo serum HCG pregnancy test at screening and urine HCG pregnancy test again on the study day.
排除标准
- •Pregnant females
- •Subjects unable to give voluntary informed consent
- •Subjects on anticoagulant drugs or anemic (anemia defined as Hcto less than 35%)
- •Subjects with a recent medical illness documented by physicians's visit or detected during the screening visit.
- •Subjects with a history of coronary heart disease.
- •Subjects with known kidney or liver disease.
- •Subjects with recent weight loss or consuming low carbohydrate diet.
研究组 & 干预措施
Blocked
Active treatment arm. Transient autonomic blockade with Trimethaphan and blood pressure restoration with L-NMMA will be used during insulin clamp
干预措施: Blocked (Drug)
Intact
Saline will be used instead of trimethaphan during insulin clamp
干预措施: Intact (Drug)
结局指标
主要结局
Insulin Resistance
时间窗: Last 30 minutes of a two hour insulin clamp
Glucose infusion rate in mg/kg/min
次要结局
未报告次要终点
研究者
Italo Biaggioni
Professor of Medicine and Pharmacology
Vanderbilt University