Effects of Exendin(9-39) on Gastroduodenal Motility

NCT00468091 | Completed Phase 1

• 3 other identifiers: MATEXDFG Ar149/1-2DFG 527/5-2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study in humans is to define the effects of the endogenous hormone GLP-1 on gastroduodenal motility and on endocrine pancreatic secretion by using the specific GLP-1 receptor antagonist exendin(9-39). To elucidate possible cholinergic pathways, we combined exendin(9-39) with the muscarinergic antagonist atropine.

Conditions

Digestive Physiology; Gastrointestinal Motility; Gastrointestinal Hormones; Glucagon-like Peptide 1; Exendin (9-39)

Keywords

GLP-1; exendin(9-39); atropine; human; motility

Outcome Measures

Primary Outcomes (1)

• Effect of exendin(9-39) on gastroduodenal motility Effect of exendin(9-39) on gastroduodenal motility with simultaneous atropine

  within the 200 min study period

Secondary Outcomes (1)

• Effect of exendin(9-39) on blood glucose levels and plasma immunoreactivities of insulin, glucagon, and pancreatic polypeptide

  within the 200 min study period

Study Arms (4)

saline-saline

PLACEBO COMPARATOR

saline IV \+ saline IV

saline-exendin(9-39)amide

ACTIVE COMPARATOR

saline IV \+ exendin(9-39)amide IV

Drug: exendin(9-39)amide

saline-atropine

ACTIVE COMPARATOR

saline IV \+ atropine IV

Drug: atropine

exendin(9-39)amide-atropine

ACTIVE COMPARATOR

exendin(9-39)amide IV \+ atropine IV

Drug: exendin(9-39)amide; Drug: atropine

Interventions

exendin(9-39)amide DRUG

exendin(9-39)amide-atropine; saline-exendin(9-39)amide

atropine DRUG

exendin(9-39)amide-atropine; saline-atropine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy volunteers
• Age 18-65 years
• Body mass index (BMI) \< 30 kg/m2
• Must have a fasting blood glucose below 100 mg/dl at screening and on all study days
• Able to provide written informed consent prior to study participation
• Able to communicate well with the investigator and comply with the requirements of the study

You may not qualify if:

• Diabetes mellitus
• Treatment with systemic steroids and thyroid hormone
• Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• Significant illness within the two weeks prior to dosing.
• Past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.
• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:
• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding
• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• history or clinical evidence of pancreatic injury or pancreatitis

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• German Research Foundation: collaborator
• Philipps University Marburg: collaborator

Study Sites (1)

Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich

Munich, 81377, Germany

Location

Related Publications (4)

• Schirra J, Sturm K, Leicht P, Arnold R, Goke B, Katschinski M. Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest. 1998 Apr 1;101(7):1421-30. doi: 10.1172/JCI1349.

  PMID: 9525985 BACKGROUND

• Schirra J, Houck P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000 May;46(5):622-31. doi: 10.1136/gut.46.5.622.

  PMID: 10764704 BACKGROUND

• Schirra J, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on motility and sensation of the proximal stomach in humans. Gut. 2002 Mar;50(3):341-8. doi: 10.1136/gut.50.3.341.

  PMID: 11839712 BACKGROUND

• Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006 Feb;55(2):243-51. doi: 10.1136/gut.2004.059741. Epub 2005 Jun 28.

  PMID: 15985560 BACKGROUND

MeSH Terms

Interventions

exendin (9-39); Atropine

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Joerg Schirra, MD

  Clinical Research Unit, Dept. of Internal Medicine II, University of Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 30, 2007
• First Posted: May 1, 2007
• Study Start: February 1, 1999
• Study Completion: September 1, 2000
• Last Updated: April 1, 2015

Record last verified: 2007-04

Locations

DE (1)