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
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Stroke
Myocardial Infarction
Drug: glucagon-like-peptide-1
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of GLP-1 on Glucose Uptake in the Brain and Heart in Healthy Subjects During Hypoglycemia Assessed by Positron Emission Tomography

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: January 2007
Study Completion Date: February 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: glucagon-like-peptide-1
intravenous infusion of 1.2pmol/kg/min for 7 hours
Placebo Comparator: P Drug: placebo
intravenous infusion of 1.2pmol/kg/min

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00418288

Locations
Denmark
Department of pharmacology, Aarhus university
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Ole E Schmitz, MD, DSc Department of pharmacology, Aarhus university
  More Information

No publications provided by University of Aarhus

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00418288     History of Changes
Other Study ID Numbers: 2005-0089
Study First Received: January 3, 2007
Last Updated: June 9, 2008
Health Authority: Denmark: Ethics Committee

Keywords provided by University of Aarhus:
GLP-1
glucose metabolism
Type 2 diabetes
brain
PET

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Infarction
Myocardial Infarction
Hypoglycemia
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Glucagon-Like Peptide 1
Glucagon
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014