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Intact Liver Innervation and Glucose and Glucagon-like Peptide-1 (GLP-1) Induced Insulin Secretion

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ClinicalTrials.gov Identifier: NCT01176708
Recruitment Status : Unknown
Verified January 2012 by Jonatan I Bagger, University Hospital, Gentofte, Copenhagen.
Recruitment status was:  Recruiting
First Posted : August 6, 2010
Last Update Posted : January 6, 2012
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen

Brief Summary:

The aim of the study is to investigate the significance of intact nerve supply to the liver for the glucagon-like peptide-1 (GLP-1) induced insulin secretion.

The hypothesis is that the effects of GLP-1 is transmitted through the GLP-1 receptor and that these effects involve sensory afferent neurons, probably primarily parasympathetic.


Condition or disease Intervention/treatment Phase
Liver Transplantation Drug: dipeptidyl peptidase 4 (DPP4) inhibitor Other: oral glucose Other: intravenous glucose Not Applicable

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.

The aim of this study is to investigate the significance of intact liver innervation for the GLP-1 induced insulin secretion in liver transplanted patients; kidney transplanted control patients matched for immunosuppressive treatment, age, gender and body weight; and ten control persons matched for age, gender and body weight.

The insulin secretion will be evaluated from blood samples that will be analyzed for insulin and c-peptide.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Significance of Intact Liver Innervation for the Glucose and GLP-1 Induced Insulin Secretion
Study Start Date : July 2009
Estimated Primary Completion Date : August 2012
Estimated Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Liver transplanted
10 Liver transplanted patients
Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol
Other Name: Panodil
Other: intravenous glucose
1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test
Other Name: Panodil
Experimental: Kidney transplanted
10 kidney transplanted individuals
Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol
Other Name: Panodil
Other: intravenous glucose
1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test
Other Name: Panodil
Experimental: Healthy controls
10 healthy controls
Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol
Other Name: Panodil
Other: intravenous glucose
1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test
Other Name: Panodil



Primary Outcome Measures :
  1. insulin secretion [ Time Frame: four hours ]
    The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated


Secondary Outcome Measures :
  1. plasma glucose [ Time Frame: 20 time points within four hours ]
    20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  2. plasma GLP-1 [ Time Frame: 12 time points within four hours ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  3. plasma GIP [ Time Frame: 12 time points within four hours ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  4. plasma glucagon [ Time Frame: 12 time points within four hours ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  5. plasma GLP-2 [ Time Frame: 12 time points within four hours ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour.

  6. plasma PYY [ Time Frame: 12 time points within four hours ]
    12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01176708


Contacts
Contact: Astrid Plamboeck, M.D. +45 26208174 astridp@sund.ku.dk

Locations
Denmark
Department of Internal Medicine F' laboratory Recruiting
Hellerup, Copenhagen, Denmark, 2900
Contact: Astrid Plamboeck, M.D.    +45 26208174    astridp@sund.ku.dk   
Contact: Tina Vilsbøll, M.D.    +45 39772461    tivi@geh.regionh.dk   
Principal Investigator: Astrid Plamboeck, M.D.         
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen

Responsible Party: Jonatan I Bagger, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01176708     History of Changes
Other Study ID Numbers: Transplant isoglycemia (AP)
First Posted: August 6, 2010    Key Record Dates
Last Update Posted: January 6, 2012
Last Verified: January 2012

Keywords provided by Jonatan I Bagger, University Hospital, Gentofte, Copenhagen:
liver transplantation
kidney transplanted
glucagon-like peptide-1
insulin secretion
vagotomy

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