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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: benzocaine; Other: placebo

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appetite, Hunger, and GI symptoms	Visual Analog Scales (Likert)	5 Hours

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Sinju Sundaresan, PhD, Vanderbilt University Medical Center; Principal Investigator: Naji N Abumrad, MD, Vanderbilt University Medical Center; Study Director: Kala Dixon, MS, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 8, 2022
• Study Completion (Actual): December 8, 2022

Study Registration Dates

• First Submitted: August 25, 2015
• First Submitted That Met QC Criteria: August 31, 2015
• First Posted (Estimate): September 1, 2015

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Normal Body Weight
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Benzocaine
• Other Study ID Numbers: 131032; R01DK100431 (U.S. NIH Grant/Contract)