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

Stroke Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00418288
• Other study ID #: 2005-0089
• Status: Completed
• Phase: N/A
• First received: January 3, 2007
• Last updated: June 9, 2008
• Start date: January 2007
• Est. completion date: February 2008

Study information

• Verified date: June 2008
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 2008
• Est. primary completion date: October 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Hypoglycemia
• Myocardial Infarction
• Stroke
• Type 2 Diabetes

Intervention

Drug:
• glucagon-like-peptide-1
intravenous infusion of 1.2pmol/kg/min for 7 hours
• placebo
intravenous infusion of 1.2pmol/kg/min

Locations

Country	Name	City	State
Denmark	Department of pharmacology, Aarhus university	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The acute effect of GLP-1 on glucose uptake in the brain		1 hour
Primary	The acute effect of GLP-1 on glucose uptake in the heart		1 hour
Secondary	The acute effect of GLP-1 on glucose metabolic rate in the brain		1 hour
Secondary	The acute effect of GLP-1 on intracerebral glucose concentration		1 hour
Secondary	The acute effect of GLP-1 on lumped constant in the brain		1 hour