The Effect of GLP-1 on the Inhibition of Glucagon Secretion

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jonatan I Bagger, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01507597
First received: December 13, 2011
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

Diabetes(both types) are recognized by high levels of glucagon in the circulation.

Glucagon is known to increase blood glucose, and might therefore contribute to the respective diseases. Under some circumstances the gut hormone GLP-1 inhibits the glucagon secretion.

The investigators aim to identify the impact of GLP-1 on the glucagon secretion, at increasing blood glucose levels in healthy subjects, in patients with type 2 diabetes, and in patients with type 1 diabetes.

The investigators think that the effect of GLP-1 on the glucagon secretion might be dependent of blood glucose levels.


Condition Intervention
Type 2 Diabetes
Type 1 Diabetes
Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))
Drug: NaCl

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Plasma Glucagon response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  • Plasma GLP-1 response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  • Plasma Glucose response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session


Secondary Outcome Measures:
  • Resting Metabolic Rate response to the GLP-1 infusion / glucose clamp [ Time Frame: at 0, 120, and 180 min ] [ Designated as safety issue: No ]
    Assessed by indirect calorimetry during the GLP-1 infusion / glucose clamp-session

  • Hunger scores response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    Assessed by VAS during the 210 min GLP-1 infusion / glucose clamp-session

  • plasma Insulin response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  • plasma GIP response to the GLP-1 infusion / glucose clamp [ Time Frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min ] [ Designated as safety issue: No ]
    The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session

  • Food Intake [ Time Frame: at 210 min ] [ Designated as safety issue: No ]
    Assessed by ad'libitum meal after the 210 min GLP-1 infusion / glucose clamp.


Enrollment: 30
Study Start Date: December 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Healthy Subjects Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: NaCl
Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)
Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

T2DM Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: NaCl
Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)
Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

T1DM Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: NaCl
Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)
Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.4 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)

Drug: Native human Glucagon-like Peptide-1 ( GLP-1(7-36))

Continuous iv. infusion of the native gut hormone GLP-1 (0.8 pmol/kg/min) for 210 minutes.

Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)


  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patients with T2DM

  • Above the age of 35 years, treatment with diet or oral anti-diabetic medication. Diagnosed with T2DM in at leat three months in advance(WHO criterion)
  • Normal hemoglobin
  • Informed content Patients with T1DM
  • T1DM (WHO criterion)
  • Plasma-C-peptid negative due to arginin-test
  • Normal hemoglobin
  • age> 18 years
  • Informed content Healthy subjects
  • Normal fasting plasma glucose and normal glucose tolerance (WHO criterion)
  • Normal hemoglobin
  • Age >18 years
  • Informed content

Exclusion Criteria:

Patients with T2DM

  • Treatment with glitazones and/or gliptins
  • Inflammatory bowels disease
  • previous bowel resection with or without stomy
  • Nephropathy (serum creatinin >150 µM and/or albuminuria)
  • Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
  • Medical treatment impossible to break for 12h.
  • Age >80 years Patients with T1DM
  • Overweight (BMI >30 kg/m2)
  • Inflammatory bowels disease
  • previous bowel resection with or without stomy
  • Nephropathy (serum creatinin >150 µM and/or albuminuria)
  • Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
  • Medical treatment impossible to break for 12h (except treatment with insulin).
  • Age >80 years

Healthy subjects

  • Diabetes
  • Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)
  • First order relatives with diabetes
  • Overweight (BMI >30 kg/m2)
  • Inflammatory bowels disease
  • previous bowel resection with or without stomy
  • Nephropathy (serum creatinin >150 µM and/or albuminuria)
  • Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) >2×normal values)
  • Medical treatment impossible to break for 12h.
  • Age >80 years
  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: NCT01507597

Locations
Denmark
Gentofte University Hospital
Hellerup, Denmark, DK-2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
  More Information

No publications provided

Responsible Party: Jonatan I Bagger, Principal Investigator, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01507597     History of Changes
Other Study ID Numbers: GlukaStase, H-3-2011-088
Study First Received: December 13, 2011
Last Updated: December 9, 2013
Health Authority: Denmark: National Board of Health
Denmark: Danish Medicines Agency

Keywords provided by University Hospital, Gentofte, Copenhagen:
Glucagon-like peptide-1
Glucagon
Normal physiology
T2DM
T1DM

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014