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

Sponsor
University Hospital, Gentofte, Copenhagen (Other)
Overall Status
Unknown status
CT.gov ID
NCT01176890
Collaborator
University of Copenhagen (Other)
30
1
3
53
0.6

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Jul 1, 2008
Actual Primary Completion Date :
Aug 1, 2011
Anticipated Study Completion Date :
Dec 1, 2012

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Panodil
  • Outcome Measures

    Primary Outcome Measures

    1. Gastric emptying [four hours]

      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

    2. Appetite [four hours]

      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)

    3. Food intake [five hours]

      After the liquid meal test, the volunteers will be offered a meal to assessed their ad libitum food intake

    Secondary Outcome Measures

    1. plasma glucose [four hours]

    2. serum insulin and c-peptide [four hours]

    3. plasma glucagon [four hours]

    4. plasma GLP-1 [four hours]

    5. endogenous GLP-1 [four hours]

      endogenous GLP-1 will be assessed as plasma GLP-2 concentration

    6. plasma GIP [four hours]

    7. serum paracetamol [four hours]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Locations

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jonatan I Bagger, MD, University Hospital, Gentofte, Copenhagen
    ClinicalTrials.gov Identifier:
    NCT01176890
    Other Study ID Numbers:
    • Truncated mealtest (AP)
    First Posted:
    Aug 6, 2010
    Last Update Posted:
    Dec 7, 2012
    Last Verified:
    Dec 1, 2012
    Keywords provided by Jonatan I Bagger, MD, University Hospital, Gentofte, Copenhagen

    Study Results

    No Results Posted as of Dec 7, 2012