Nutrient Sensing in the Duodenum

Duodenal Lipid Sensing and Nutrient Absorption

Preliminary studies in humans suggest that the presence of lipids in the gut can modify glucose absorption. The overall hypothesis of this proposal is that long chain fatty acid sensing in the duodenum has a significant role in modifying nutrient (glucose and amino acid) absorption from the GI tract through a gut-brain-gut axis.

Study Overview

• Status: Completed
• Conditions: The Effect of LCFA on Nutrient Absorption
• Intervention / Treatment: Drug: Benzocaine Infusion into Duodenum

Detailed Description

The investigator will conduct a study in 20 lean (BMI = 19-27 kg/m2) subjects involving intravenous (IV) and intraduodenal (ID) infusions of glucose tracers or amino acid tracers and measurement of tracer rate of appearance in the plasma. An ID infusion of LCFA will allow the investigators to determine if LCFA can alter nutrient absorption and glucose and amino acid metabolism. Benzocaine will be added to the ID infusion of LCFA to inhibit nerve terminals in the duodenum thereby preventing gut-brain communication. Plasma levels of glucose and amino acid tracers, glucose oxidation (13CO2 breath test), gut hormones (CCK, GIP, PYY, GLP-1, ghrelin), and bioactive lipids (N-acyl phosphatidylethanolamines, NAPEs) will be measured during all infusion periods.

• Study Type: Interventional
• Enrollment (Actual): 16
• 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: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI = 19-27 kg/m2
• 30-55 years of age

Exclusion Criteria:

• Contraindication for nasal tube placement (e.g. deviated 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, Barrett's esophagus
• Type 1 or type 2 diabetes
• Gastroenteritis (diarrhea and/or vomiting) or constipation within the past week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Benzocaine Infusion into Duodenum; The investigator will conduct a study in 20 lean (BMI = 19-27 kg/m2) subjects involving intravenous (IV) and intraduodenal (ID) infusions of glucose tracers or amino acid traces and measurement of tracer rate of appearance in the plasma. An ID infusion of LCFA will allow the investigators to determine if LCFA can alter nutrient absorption and glucose and amino acid metabolism. Benzocaine will be added to the ID infusion of LCFA to inhibit nerve terminals in the duodenum thereby preventing gut-brain communication. Plasma levels of glucose and amino acid tracers, glucose oxidation (13CO2 breath test), gut hormones (CCK, GIP, PYY, GLP-1, ghrelin), and bioactive lipids (N-acyl phosphatidylethanolamines, NAPEs) will be measured during all infusion periods.

Drug: Benzocaine Infusion into Duodenum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutrient Absorption	Stable isotope tracers (glucose or amino acid) will be administered intravenously (IV) and intraduodenally (ID) and tracer rate of appearance in the plasma will be measured.	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substrate Oxidation	Oxidation of intraduodenally administered glucose or amino acid will be determined by the amount of 13C recovered from expired air.	6 hours
Gut Hormone Levels	Plasma levels of gut hormones will be measured by standard RIA or ELISA assays	6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioactive Lipids	Plasma levels of N-acyl phosphatidylethanolamines (NAPES)will be measured by LC-MS	6 hours

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Robyn Tamboli, PhD, Vanderbilt University Medical Center; Study Director: Naji Abumrad, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): October 27, 2014
• Study Completion (Actual): October 27, 2014

Study Registration Dates

• First Submitted: September 24, 2012
• First Submitted That Met QC Criteria: September 24, 2012
• First Posted (Estimated): September 26, 2012

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Nutrient absorption; Duodenal feeding tube; Gut-brain-gut axis
• 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: IRB #121111; P30DK058404 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No