Intact Vagal Innervation 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:
NCT01176890
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 Glucagon-like peptide-1 (GLP-1) in respect to gastric emptying, appetite and food intake.

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


Condition Intervention
Vagotomy, Truncal
Drug: GLP-1
Other: Saline

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Significance of Intact Vagal Innervation for the GLP-1 Induced Inhibition of Gastric Emptying, Appetite and Food Intake

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Gastric emptying [ Time Frame: four hours ] [ Designated as safety issue: No ]
    Gastric emptying will be assessed using a liquid meal with 1.5 g paracetamol added and continuous blood sampling for measuring paracetamol concentration during four hours

  • Appetite [ Time Frame: four hours ] [ Designated as safety issue: No ]
    Hunger, satiation, and fullness will be assessed before, during and after a liquid meal with 1.5 g paracetamol added using a visual analog scale (VAS)

  • Food intake [ Time Frame: five hours ] [ Designated as safety issue: No ]
    After the liquid meal test, the volunteers will be offered a meal to assessed their ad libitum food intake


Secondary Outcome Measures:
  • plasma glucose [ Time Frame: four hours ] [ Designated as safety issue: No ]
  • serum insulin and c-peptide [ Time Frame: four hours ] [ Designated as safety issue: No ]
  • plasma glucagon [ Time Frame: four hours ] [ Designated as safety issue: No ]
  • plasma GLP-1 [ Time Frame: four hours ] [ Designated as safety issue: No ]
  • endogenous GLP-1 [ Time Frame: four hours ] [ Designated as safety issue: No ]
    endogenous GLP-1 will be assessed as plasma GLP-2 concentration

  • plasma GIP [ Time Frame: four hours ] [ Designated as safety issue: No ]
  • serum paracetamol [ Time Frame: four hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: July 2008
Estimated Study Completion Date: December 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vago
Truncally vagotomized subjects (due to duodenal ulcer operation)
Drug: GLP-1

1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

Other Name: Panodil
Other: Saline

Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

Other Name: Panodil
Experimental: Cardia
truncally vagotomized subjects (due to esophagus resection)
Drug: GLP-1

1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

Other Name: Panodil
Other: Saline

Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

Other Name: Panodil
Experimental: Healthy controls
Healthy control subjects
Drug: GLP-1

1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

Other Name: Panodil
Other: Saline

Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes.

After four hours an ad libitum meal will be supplied

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 GLP-1 on the food intake, gastric emptying (GE) and appetite.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • truncal vagotomy
  • normal hemoglobin
  • informed consent
  • Age, gender and weight matched controls
  • normal hemoglobin
  • informed consent

Exclusion Criteria:

  • type 1 diabetes mellitus or type 2 diabetes mellitus
  • body mass index > 30 kg/m2
  • inflammatory bowel disease
  • intestinal resection
  • nephropathy (serum creatinine > 150 µM and/or albuminuria)
  • liver disease (ALAT and/or ASAT > 2 x normal value)
  • 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: NCT01176890

Locations
Denmark
Department of Internal Medicine F' laboratory
Hellerup, Copenhagen, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen
Investigators
Principal Investigator: Astrid Plamboeck, M.D. University Hospital, Gentofte, Copenhagen
Study Director: Tina Vilsbøll, M.D. 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: NCT01176890     History of Changes
Other Study ID Numbers: Truncated mealtest (AP)
Study First Received: August 5, 2010
Last Updated: December 6, 2012
Health Authority: Denmark: Danish Dataprotection Agency

Keywords provided by University Hospital, Gentofte, Copenhagen:
truncal vagotomy
GLP-1
gastric emptying
appetite
food intake

Additional relevant MeSH terms:
Glucagon-Like Peptide 1
Glucagon
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014