Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Glucose and Free Fatty Acids
研究概览
简要总结
The overall hypothesis of this proposal is that nutrient sensing in the foregut regulates metabolic hormone secretion and nutrient metabolism via enteric neural signals, and these mechanisms might be defective in obesity.
详细描述
The study proposes two specific aims Aim 1 will determine if blocking enteric neuronal signaling will alter: a) circulating levels of nutrient substrates and secretion of hormones that regulate nutrient metabolism; and b) glucose and fatty acid absorption, production, and utilization.
Obese (BMI = 30-50 kg/m2) subjects will be studied. The topical anesthetic benzocaine will be infused into the duodenum prior to infusion of glucose and oleic acid into the duodenum. Duodenal infusions with a naso-intestinal feeding tube will circumvent the confounding effects of gastric emptying on the metabolic responses to a meal. Substrates (glucose, free fatty acids), and lipoproteins) and hormones will be measured by standard biochemical and immunological methods. Aim 2 will determine if enteric neural signals regulate appetite. The studies will be carried out in both lean and obese humans and the procedure will be performed as described above. In addition, the subjects will be asked to use a visual analog scale to estimate their level of appetite before, during and after enteral infusions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 19 - 25 kg/m2 or 30 - 50 kg/m2
- •Age 20 - 50 years
排除标准
- •Contraindication to a nasoduodenal feeding tube (e.g., deviated nasal septum, prior upper gastrointestinal bleed, or history of easy bleeding)
- •Prior gastric or intestinal surgery or pancreas resection
- •Females with a positive pregnancy test
- •Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), celiac sprue
- •Type 1 or type 2 diabetes
- •Recent presence of or treatment for gastroenteritis (diarrhea and/or vomiting), constipation, or upper respiratory infection
- •Abnormal electrocardiogram
- •Prior adverse reaction to anesthesia
- •Tobacco use
研究组 & 干预措施
placebo
Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes)
干预措施: placebo (Other)
benzocaine
0.5% benzocaine solution in saline/hydrochloric acid administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes)
干预措施: benzocaine (Drug)
结局指标
主要结局
Glucose and Free Fatty Acids
时间窗: 5 Hours
Plasma levels
Gastrointestinal Hormones
时间窗: 5 Hours
Plasma levels of Cholecystokinin, gastric inhibitory peptide and glucagon like peptide and Ghrelin
Pancreatic Hormones
时间窗: 5 Hours
Plasma levels of Insulin, C-peptide, Glucagon
次要结局
- Fat Metabolism(5 Hours)
- Glucose Metabolism(5 Hours)
研究者
Naji Abumrad
Professor
Vanderbilt University Medical Center