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

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Enrolling by invitation
CT.gov ID
NCT02537314
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
45
Enrollment
1
Location
2
Arms
88
Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Single (Participant)
Primary Purpose:
Basic Science
Official Title:
Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans
Study Start Date :
Sep 1, 2015
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Gastrointestinal Hormones [5 Hours]

      Plasma levels of Cholecystokinin, gastric inhibitory peptide and glucagon like peptide and Ghrelin

    2. Pancreatic Hormones [5 Hours]

      Plasma levels of Insulin, C-peptide, Glucagon

    3. Glucose and Free Fatty Acids [5 Hours]

      Plasma levels

    Secondary Outcome Measures

    1. Glucose Metabolism [5 Hours]

      Glucose tracer kinetics ([3-tritiated] glucose and [U-13C-carbon] oleate)

    2. Fat Metabolism [5 Hours]

      Oleate tracer kinetics ([U-13 C-carbon] oleate)

    Other Outcome Measures

    1. Appetite, Hunger, and GI symptoms [5 Hours]

      Visual Analog Scales (Likert)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Vanderbilt University Medical Center Nashville Tennessee United States 37232

    Sponsors and Collaborators

    • Vanderbilt University Medical Center
    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Naji Abumrad, Professor, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT02537314
    Other Study ID Numbers:
    • 131032
    • R01DK100431
    First Posted:
    Sep 1, 2015
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Naji Abumrad, Professor, Vanderbilt University Medical Center
    Normal Body Weight
    Additional relevant MeSH terms:
    Benzocaine

    Study Results

    No Results Posted as of Mar 31, 2022