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

Phase 1

Completed

• Conditions: Functional Gastrointestinal Disorders
• Interventions: Biological: Intravenous saline; Biological: GLP-1

• Registration Number: NCT02731664
• Lead Sponsor: Uppsala University

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2016-03-06
• Study First Submitted QC: 2016-04-06
• Study First Posted: 2016-04-07
• Primary Completion: 2017-08
• Study Completion: 2017-08
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-07
• Last Update Posted: 2018-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Healthy volunteers over 18 years of age.

Exclusion Criteria

• Any medical condition.
• Any drug treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control	Intravenous saline	Intravenous saline
GLP-1	GLP-1	Intravenous infusion of GLP-1 at 0.7 and 1.2 mol/kg per minute

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Uppsala University; 🇸🇪 Uppsala, Uppsala County, Sweden