The Effect of GLP-1 on Glucose Uptake in the Brain and Heart in Healthy Men During Hypoglycemia

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00418288
First received: January 3, 2007
Last updated: June 9, 2008
Last verified: June 2008

January 3, 2007
June 9, 2008
January 2007
October 2007   (final data collection date for primary outcome measure)
  • The acute effect of GLP-1 on glucose uptake in the brain [ Time Frame: 1 hour ]
  • The acute effect of GLP-1 on glucose uptake in the heart [ Time Frame: 1 hour ]
  • The acute effect of GLP-1 on glucose uptake in the brain
  • The acute effect of GLP-1 on glucose uptake in the heart
Complete list of historical versions of study NCT00418288 on ClinicalTrials.gov Archive Site
  • The acute effect of GLP-1 on glucose metabolic rate in the brain [ Time Frame: 1 hour ]
  • The acute effect of GLP-1 on intracerebral glucose concentration [ Time Frame: 1 hour ]
  • The acute effect of GLP-1 on lumped constant in the brain [ Time Frame: 1 hour ]
  • The acute effect of GLP-1 on glucose metabolic rate in the brain
  • The acute effect of GLP-1 on intracerebral glucose concentration
  • The acute effect of GLP-1 on lumped constant in the bra
Not Provided
Not Provided
 
The Effect of GLP-1 on Glucose Uptake in the Brain and Heart in Healthy Men During Hypoglycemia
The Effect of GLP-1 on Glucose Uptake in the Brain and Heart in Healthy Subjects During Hypoglycemia Assessed by Positron Emission Tomography

Type 2 diabetes mellitus, T2D is a disease characterized by an immense growing prevalence world wide with an increased risk of myocardial infarction and stroke. GLP-1 has convincing effects on the high glucose levels in type 2 diabetic patients and is well tolerated. New animal studies indicate a protective effect of GLP-1 in the brain and the heart. The mechanism behind this is yet not known.

The study hypothesis is that during hypoglycaemia GLP-1 will stimulate glucose-uptake in the brain and heart independent of insulin and thereby exert protective effects in the brain.

Type 2 diabetes mellitus, T2D is a disease characterized by an immense growing prevalence world wide. T2D is associated with a three-fold increase in cardiovascular complications (myocardial infarction and stroke) leading to significantly higher morbidity and mortality in this group of patients. The prospective British Diabetes Study (UKPDS) showed that neither diet alone nor the pharmaceutical treatment utilized (Sulphonylurea, Metformin, Insulin) were able to reduce these macrovascular complications. GLP-1 (glucagon-like-peptide-1)is an incretin with convincing effects on glycaemia in type 2 diabetic patients with little or no risk of hypoglycaemia. New research in animal models has shown a potential protective effect in the brain and heart in association with ischaemic damage. The mechanism behind this protective effect is not known. During hypoglycaemia the brain lacks glucose which is the main fuel for sufficient brain function. The brain will compensate by increasing glucose uptake across the blood brain barrier and similarly in the heart.

The effect of native GLP-1 on glucose uptake in the brain and heart will by visualized by fluoro-deoxy-glucose FDG-PET-scan during hypoglycaemia in healthy men. At the same time a pancreatic/pituitary clamp will be performed. The hypothesis is that GLP-1 directly will stimulate glucose uptake independent of the pancreatic hormones and through this mechanism exert neuro- and cardioprotective actions.

Comparisons: FDG-uptake in the brain and heart with GLP-1 infusion compared to placebo.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Type 2 Diabetes
  • Stroke
  • Myocardial Infarction
  • Drug: glucagon-like-peptide-1
    intravenous infusion of 1.2pmol/kg/min for 7 hours
  • Drug: placebo
    intravenous infusion of 1.2pmol/kg/min
  • Active Comparator: A
    Intervention: Drug: glucagon-like-peptide-1
  • Placebo Comparator: P
    Intervention: Drug: placebo
Gejl M, Lerche S, Mengel A, Møller N, Bibby BM, Smidt K, Brock B, Søndergaard H, Bøtker HE, Gjedde A, Holst JJ, Hansen SB, Rungby J. Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia. PLoS One. 2014 Jan 6;9(1):e83758. doi: 10.1371/journal.pone.0083758. eCollection 2014.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
February 2008
October 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy men
  • Age 20-50 years
  • Caucasian
  • BMI 20-30 kg/m2

Exclusion Criteria:

  • Diabetes in subject and 1.degree relatives
  • Any disease of clinical relevance
Male
20 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00418288
2005-0089
No
Not Provided
University of Aarhus
Not Provided
Principal Investigator: Ole E Schmitz, MD, DSc Department of pharmacology, Aarhus university
University of Aarhus
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP