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GLP-1 Inhibits Prandial Antro-duodeno-jejunal Motility in Humans (GLPMOT)

Primary Purpose

Functional Gastrointestinal Disorders

Status

Completed

Phase

Phase 1

Locations

Sweden

Study Type

Interventional

Intervention

GLP-1

Intravenous saline

About this trial

This is an interventional basic science trial for Functional Gastrointestinal Disorders focused on measuring Irritable bowel syndrome, Functional dyspepsia, Gastric emptying, Gastrointestinal peptide hormones

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers over 18 years of age.

Exclusion Criteria:

Any medical condition.
Any drug treatment.

Sites / Locations

Uppsala University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GLP-1

Control

Arm Description

Intravenous infusion of GLP-1 at 0.7 and 1.2 mol/kg per minute

Intravenous saline

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT02731664

First Posted

March 6, 2016

Last Updated

August 7, 2018

Sponsor

Uppsala University

Collaborators

Karolinska Institutet

1. Study Identification

Unique Protocol Identification Number

NCT02731664

Brief Title

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

Acronym

GLPMOT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

September 2012 (Actual)

Primary Completion Date

August 2017 (Actual)

Study Completion Date

August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Uppsala University

Collaborators

Karolinska Institutet

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Functional Gastrointestinal Disorders

Keywords

Irritable bowel syndrome, Functional dyspepsia, Gastric emptying, Gastrointestinal peptide hormones

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GLP-1

Arm Type

Experimental

Arm Description

Intravenous infusion of GLP-1 at 0.7 and 1.2 mol/kg per minute

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

Intravenous saline

Intervention Type

Biological

Intervention Name(s)

GLP-1

Other Intervention Name(s)

Glucagon-like peptide-1

Intervention Description

Intravenous infusion of GLP-1

Intervention Type

Biological

Intervention Name(s)

Intravenous saline

Intervention Description

Control

Primary Outcome Measure Information:

Title

Motility index (measure of contraction amplitude x duration; area for mmHg x sec)

Description

Inhibition of prandially increased motility index (motor activity in the antrum and upper small intestine).

Time Frame

60 minutes

Secondary Outcome Measure Information:

Title

Smooth muscle relaxation induced by GLP-1

Description

Separate experiments in vitro: GLP-1-induced inhibition of bethanechol-stimulated smooth muscle strips to characterize GLP-1's pharmacological action.

Time Frame

6 hours

Title

Presence of GLP-1 and GLP-2 receptors in gastric and small bowel tissue

Description

Separate experiments in vitro: Antibody staining of gastric and small bowel tissue for receptors of GLP-1 and GLP-2

Time Frame

1 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Per M. Hellström, MD, PhD

Organizational Affiliation

Uppsala University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Uppsala University

City

Uppsala

State/Province

Uppsala County

ZIP/Postal Code

75185

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

On request.

Citations:

PubMed Identifier

20584260

Citation

Edholm T, Degerblad M, Gryback P, Hilsted L, Holst JJ, Jacobsson H, Efendic S, Schmidt PT, Hellstrom 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.

Results Reference

background

PubMed Identifier

18945254

Citation

Hellstrom PM, Hein J, Bytzer P, Bjornsson 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.

Results Reference

background

PubMed Identifier

18298441

Citation

Hellstrom PM, Naslund 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. Neurogastroenterol Motil. 2008 Jun;20(6):649-59. doi: 10.1111/j.1365-2982.2007.01079.x. Epub 2008 Feb 19.

Results Reference

result

PubMed Identifier

29177486

Citation

Halim MA, Degerblad M, Sundbom M, Karlbom U, Holst JJ, Webb DL, Hellstrom PM. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. J Clin Endocrinol Metab. 2018 Feb 1;103(2):575-585. doi: 10.1210/jc.2017-02006.

Results Reference

derived

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

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