Obesity
Conditions
Keywords
Normal Body Weight
Brief summary
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.
Detailed description
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.
Interventions
DRUGbenzocaine
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)
OTHERplacebo
Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 19 - 25 kg/m2 or 30 - 50 kg/m2 * Age 20 - 50 years
Exclusion criteria
* 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 * Anemia * Abnormal electrocardiogram * Prior adverse reaction to anesthesia * Tobacco use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Hormones | 5 Hours | Plasma levels of Cholecystokinin, gastric inhibitory peptide and glucagon like peptide and Ghrelin |
| Pancreatic Hormones | 5 Hours | Plasma levels of Insulin, C-peptide, Glucagon |
| Glucose and Free Fatty Acids | 5 Hours | Plasma levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Metabolism | 5 Hours | Glucose tracer kinetics (\[3-tritiated\] glucose and \[U-13C-carbon\] oleate) |
| Fat Metabolism | 5 Hours | Oleate tracer kinetics (\[U-13 C-carbon\] oleate) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Appetite, Hunger, and GI symptoms | 5 Hours | Visual Analog Scales (Likert) |
Countries
United States
Outcome results
None listed