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

Phase 1

Completed

• Conditions: Obesity
• Interventions: Other: placebo; Drug: benzocaine

• Registration Number: NCT02537314
• Lead Sponsor: Vanderbilt University Medical Center

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.

Study Timeline

• Study First Submitted: 2015-08-25
• Study First Submitted QC: 2015-08-31
• Study Start: 2015-09
• Study First Posted: 2015-09-01
• Status Verified: 2022-12
• Primary Completion: 2022-12-08
• Study Completion: 2022-12-08
• Last Update Submitted: 2022-12-08
• Last Update Posted: 2022-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo	placebo	Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes)
benzocaine	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)

Primary Outcome Measures

Name	Time	Method
Glucose and Free Fatty Acids	5 Hours	Plasma levels
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

Secondary Outcome Measures

Name	Time	Method
Fat Metabolism	5 Hours	Oleate tracer kinetics (\[U-13 C-carbon\] oleate)
Glucose Metabolism	5 Hours	Glucose tracer kinetics (\[3-tritiated\] glucose and \[U-13C-carbon\] oleate)

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States