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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK100431 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| benzocaine | Active Comparator | 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 Comparator | Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| benzocaine | 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) |
|
| 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 |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Appetite, Hunger, and GI symptoms | Visual Analog Scales (Likert) | 5 Hours |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sinju Sundaresan, PhD | Vanderbilt University Medical Center | Principal Investigator |
| Naji N Abumrad, MD | Vanderbilt University Medical Center | Principal Investigator |
| Kala Dixon, MS | Vanderbilt University Medical Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37661107 | Background | 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. |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D001566 | Benzocaine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
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| placebo | Other | Placebo (saline) solution administered by intraduodenal infusion one time (6 ml bolus followed by 75 ml/hour for 105 minutes) |
|
|
| 5 Hours |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |