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

Stroke Clinical Trial

Official title:

The Effect of GLP-1 on Glucose Uptake in the CNS and Heart in Healthy Subjects During Normoglycaemia Assessed by Positron Emission Tomografi

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00256256
• Other study ID #: 2005-0079
• Status: Completed
• Phase: N/A
• First received: November 16, 2005
• Last updated: October 29, 2007
• Start date: November 2005
• Est. completion date: January 2007

Study information

• Verified date: October 2007
• 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 GLP-1 will stimulate glucose-uptake in the brain and heart independent of insulin and thereby exert its protective effects.

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.

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 normoglycaemia in healthy young 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 its 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: January 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: Prevention

Related Conditions & MeSH terms

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

Intervention

Drug:
• glucagon-like-peptide-1
Dose: 1.2pmol/kg/min for 6 hours

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, 

References & Publications (5)

Bose AK, Mocanu MM, Carr RD, Yellon DM. Glucagon like peptide-1 is protective against myocardial ischemia/reperfusion injury when given either as a preconditioning mimetic or at reperfusion in an isolated rat heart model. Cardiovasc Drugs Ther. 2005 Jan;19(1):9-11. — View Citation

During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. Epub 2003 Aug 17. — View Citation

Holst JJ. On the physiology of GIP and GLP-1. Horm Metab Res. 2004 Nov-Dec;36(11-12):747-54. Review. — View Citation

Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004 Mar 2;109(8):962-5. Epub 2004 Feb 23. — View Citation

Perry T, Haughey NJ, Mattson MP, Egan JM, Greig NH. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep;302(3):881-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FDG-uptake in the brain and heart visualized by Positron emission tomography with and without GLP-1		After 4 hours of GLP-infusion
Secondary	Laboratory values (insulin secretion and counter-regulatory hormones)		During 7 hours of clamp and GLP-1/placebo infusion