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

Functional Gastrointestinal Disorders Clinical Trial

— GLPMOT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02731664
• Other study ID #: PRANDMOTGLP
• Status: Completed
• Phase: Phase 1
• Start date: September 2012
• Est. completion date: August 2017

Study information

• Verified date: August 2018
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers over 18 years of age.

Exclusion Criteria:

• Any medical condition.

• Any drug treatment.

Related Conditions & MeSH terms

• Digestive System Diseases
• Functional Gastrointestinal Disorders
• Gastrointestinal Diseases

Intervention

Biological:
• GLP-1
Intravenous infusion of GLP-1
• Intravenous saline
Control

Locations

Country	Name	City	State
Sweden	Uppsala University	Uppsala	Uppsala County

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Edholm T, Degerblad M, Grybäck P, Hilsted L, Holst JJ, Jacobsson H, Efendic S, Schmidt PT, Hellström PM. Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Neurogastroenterol Motil. 2010 Nov;22(11):1191-200, e315. doi: 10.1111/j.1365-2982.2010.01554.x. — View Citation

Hellström PM, Hein J, Bytzer P, Björnssön E, Kristensen J, Schambye H. Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind study. Aliment Pharmacol Ther. 2009 Jan;29(2):198-206. doi: 10.1111/j.1365-2036.2008.03870.x. Epub 2008 Oct 10. — View Citation

Hellström PM, Näslund E, Edholm T, Schmidt PT, Kristensen J, Theodorsson E, Holst JJ, Efendic S. GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome. Neurogastr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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