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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by University Hospital, Gentofte, Copenhagen.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01176708
First received: August 5, 2010
Last updated: January 5, 2012
Last verified: January 2012
  Purpose

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 Intervention
Liver Transplantation
Drug: dipeptidyl peptidase 4 (DPP4) inhibitor
Other: oral glucose
Other: intravenous 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 Significance of Intact Liver Innervation for the Glucose and GLP-1 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 glucose [ Time Frame: 20 time points within four hours ] [ Designated as safety issue: No ]
    20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

  • 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: July 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
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
Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

No publications provided

Responsible Party: Jonatan I Bagger, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01176708     History of Changes
Other Study ID Numbers: Transplant isoglycemia (AP)
Study First Received: August 5, 2010
Last Updated: January 5, 2012
Health Authority: Denmark: Danish Dataprotection Agency

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

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

ClinicalTrials.gov processed this record on April 16, 2014