GLP-1 Inhibits Prandial Antro-duodeno-jejunal Motility in Humans

Study Overview
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Brief Summary
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The inhibitory effect of low dose GLP-1 is investigated on prandial motility of the stomach, duodenum and jejunum in vivo in humans. Supplementary in vitro studies on the mechanism of action of the GLP-1 inhibition of motility as carried out on muscle strips from the upper gastrointestinal tract in man.

Detailed Description
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Twelve healthy volunteers will undergo antroduodenojejunal manometry. Baseline recording with infusion of saline for 1 hour is compared with infusion of GLP-1 0.7 and 1.2 pmol per kg minute for another 1 hour. Plasma GLP-1 and GLP-2 is measured by RIA. Responses to GLP-1 will be measured after food intake as prandial response to GLP-1. The outcome will be evaluated as change in motility index from baseline to meal-stimulated conditions and during influence of GLP-1. Further in vitro studies of gastrointestinal muscle strips, precontracted with bethanechol or electric field stimulation, are planned to investigate the response to GLP-1 or GLP-1 analogue ROSE-010. GLP-1 and GLP-2 receptor immunoreactivity is localized by immunohistochemistry. Receptor mediated mechanisms are studied with GLP-1 receptor blocker exendin(9-39)amide, nitro-monomethyl arginine to block nitric oxide synthase and tetrodotoxin to block sodium channels and nerve conduction.

Official Title
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GLP-1 Inhibits Prandial Antro-duodeno-jejunal Motility in Humans: Native GLP-1 Compared With Analogue ROSE-010 in Vitro

Conditions
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Functional Gastrointestinal Disorders

Intervention / Treatment
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* Biological: GLP-1
* Biological: Intravenous saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers over 18 years of age. Exclusion Criteria: Any medical condition. Any drug treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLP-1<br>Intravenous infusion of GLP-1 at 0.7 and 1.2 mol/kg per minute | Biological: GLP-1<br>* Intravenous infusion of GLP-1<br>* Other names: Glucagon-like peptide-1;|
| Placebo Comparator: Control<br>Intravenous saline | Biological: Intravenous saline<br>* Control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motility index (measure of contraction amplitude x duration; area for mmHg x sec) | Inhibition of prandially increased motility index (motor activity in the antrum and upper small intestine). | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smooth muscle relaxation induced by GLP-1 | Separate experiments in vitro: GLP-1-induced inhibition of bethanechol-stimulated smooth muscle strips to characterize GLP-1's pharmacological action. | 6 hours | 
| Presence of GLP-1 and GLP-2 receptors in gastric and small bowel tissue | Separate experiments in vitro: Antibody staining of gastric and small bowel tissue for receptors of GLP-1 and GLP-2 | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable bowel syndrome, Functional dyspepsia, Gastric emptying, Gastrointestinal peptide hormones