Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans

Study Overview
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Brief Summary
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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
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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.

Official Title
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Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans

Conditions
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Obesity

Intervention / Treatment
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* Drug: benzocaine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: benzocaine<br>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) | Drug: benzocaine<br>* 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)<br>* Other names: ethyl 4-aminobenzoate;|
| Placebo Comparator: placebo<br>Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes) | Other: placebo<br>* Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes)<br>* Other names: NaCl, sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal Hormones | Plasma levels of Cholecystokinin, gastric inhibitory peptide and glucagon like peptide and Ghrelin | 5 Hours | 
| Pancreatic Hormones | Plasma levels of Insulin, C-peptide, Glucagon | 5 Hours | 
| Glucose and Free Fatty Acids | Plasma levels | 5 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Metabolism | Glucose tracer kinetics ([3-tritiated] glucose and [U-13C-carbon] oleate) | 5 Hours | 
| Fat Metabolism | Oleate tracer kinetics ([U-13 C-carbon] oleate) | 5 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normal Body Weight