Intact Vagal Innervation for and Glucagon-like Peptide-1 (GLP-1) Effects

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01176760
First received: August 5, 2010
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

The aim of this study is to investigate the role of transmission via the vagal nerve for the effect of glucose and Glucagon-like peptide-1 (GLP-1) in respect to insulin secretion.

The hypothesis is that a great deal of the effects of GLP-1 is mediated via the nervous system and for this reason the investigators will research individuals with and without intact nervous supply.


Condition Intervention
Vagotomy, Truncal
Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor
Other: oral glucose

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Significances of Intact Vagal Innervation for the Glucose and GLP1 Induced Insulin Secretion

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • insulin secretion [ Time Frame: four hours ] [ Designated as safety issue: No ]
    The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated


Secondary Outcome Measures:
  • plasma GLP-1 [ Time Frame: 12 time points within four hours ] [ Designated as safety issue: No ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  • plasma GIP [ Time Frame: 12 time points within four hours ] [ Designated as safety issue: No ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  • plasma glucagon [ Time Frame: 12 time points within four hours ] [ Designated as safety issue: No ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  • plasma GLP-2 [ Time Frame: 12 time points within four hours ] [ Designated as safety issue: No ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  • plasma PYY [ Time Frame: 12 time points within four hours ] [ Designated as safety issue: No ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour


Estimated Enrollment: 30
Study Start Date: August 2009
Estimated Study Completion Date: December 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vago
Truncally vagotomized subjects (due to duodenal ulcer operation)
Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor
One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3
Other Name: Galvus
Other: oral glucose
50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.
Other Name: panodil
Experimental: Cardia
Truncally vagotomized subjects (due to cardia resection)
Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor
One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3
Other Name: Galvus
Other: oral glucose
50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.
Other Name: panodil
Experimental: Ctrl
Healthy matched control subjects
Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor
One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3
Other Name: Galvus
Other: oral glucose
50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.
Other Name: panodil

Detailed Description:

GLP-1 is a potent enterogastron and incretin hormone. It is rapidly inactivated by dipeptidyl peptidase IV so only 10-15% enters the systemic circulation. This has led to the hypothesis that GLP-1 interact locally with afferent sensory nerve fibers. We investigated the role of intact vagal innervations on the effect of glucose and GLP-1 on the insulin secretion

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • normal fasting plasma glucose
  • normal hemoglobin
  • informed consent

Exclusion Criteria:

  • type 1 diabetes mellitus or type 2 diabetes mellitus
  • body mass index > 30
  • inflammatory bowel disease
  • intestinal surgery
  • serum creatinine > 250 µM and/or albuminuria
  • ALAT > 2 x normal value
  • Severe cardiac insufficiency
  • in treatment with medicine which cannot be paused for 12 hours
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176760

Locations
Denmark
Department of internal medicine F´laboratory, Gentofte Hospital
Hellerup, Copenhagen, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen
Investigators
Principal Investigator: Astrid Plamboeck, MD University Hospital, Gentofte, Copenhagen
Study Director: Tina Vilsbøll, MD, dr.med University Hospital, Gentofte, Copenhagen
  More Information

No publications provided by University Hospital, Gentofte, Copenhagen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jonatan I Bagger, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01176760     History of Changes
Other Study ID Numbers: Truncated isoglycemia
Study First Received: August 5, 2010
Last Updated: December 6, 2012
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by University Hospital, Gentofte, Copenhagen:
vagotomy
vagus
GLP-1
Insulin secretion

Additional relevant MeSH terms:
Glucagon-Like Peptide 1
Glucagon
Dipeptidyl-Peptidase IV Inhibitors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on July 09, 2014