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

NCT ID: NCT02537314

Last Updated: 2022-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2022-12-08

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.

Conditions

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Obesity

Keywords

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Normal Body Weight

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

benzocaine

Intervention Type DRUG

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)

placebo

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

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

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

Interventions

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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)

Intervention Type DRUG

placebo

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

Intervention Type OTHER

Other Intervention Names

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ethyl 4-aminobenzoate NaCl, sodium chloride

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
Minimum Eligible Age

20 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Naji Abumrad

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sinju Sundaresan, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Naji N Abumrad, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Kala Dixon, MS

Role: STUDY_DIRECTOR

Vanderbilt University Medical Center

Locations

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Sundaresan S, Johnson C, Dixon KB, Dole M, Kilkelly D, Antoun J, Flynn CR, Abumrad NN, Tamboli R. Intraduodenal nutrient infusion differentially alters intestinal nutrient sensing, appetite, and satiety responses in lean and obese subjects. Am J Clin Nutr. 2023 Sep;118(3):646-656. doi: 10.1016/j.ajcnut.2023.06.011. Epub 2023 Aug 8.

Reference Type DERIVED
PMID: 37661107 (View on PubMed)

Other Identifiers

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R01DK100431

Identifier Type: NIH

Identifier Source: secondary_id

View Link

131032

Identifier Type: -

Identifier Source: org_study_id