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

Primary Purpose

Type 2 Diabetes, Stroke, Myocardial Infarction

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
glucagon-like-peptide-1
Sponsored by
University of Aarhus
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 2 Diabetes focused on measuring type 2 diabetes, GLP-1, PET, brain, heart

Eligibility Criteria

20 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Department of pharmacology, Aarhus university

Outcomes

Primary Outcome Measures

FDG-uptake in the brain and heart visualized by Positron emission tomography with and without GLP-1

Secondary Outcome Measures

Laboratory values (insulin secretion and counter-regulatory hormones)

Full Information

First Posted
November 16, 2005
Last Updated
October 29, 2007
Sponsor
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT00256256
Brief Title
The Effect of GLP-1 on Glucose Uptake in the Brain and Heart in Healthy Men
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Aarhus

4. Oversight

5. Study Description

Brief 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.
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Stroke, Myocardial Infarction
Keywords
type 2 diabetes, GLP-1, PET, brain, heart

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
glucagon-like-peptide-1
Intervention Description
Dose: 1.2pmol/kg/min for 6 hours
Primary Outcome Measure Information:
Title
FDG-uptake in the brain and heart visualized by Positron emission tomography with and without GLP-1
Time Frame
After 4 hours of GLP-infusion
Secondary Outcome Measure Information:
Title
Laboratory values (insulin secretion and counter-regulatory hormones)
Time Frame
During 7 hours of clamp and GLP-1/placebo infusion

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ole Schmitz, MD,professor
Organizational Affiliation
Department of pharmacology, Aarhus university
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of pharmacology, Aarhus university
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
12925848
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. doi: 10.1038/nm919. Epub 2003 Aug 17.
Results Reference
background
PubMed Identifier
14981009
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. doi: 10.1161/01.CIR.0000120505.91348.58. Epub 2004 Feb 23.
Results Reference
background
PubMed Identifier
15655703
Citation
Holst JJ. On the physiology of GIP and GLP-1. Horm Metab Res. 2004 Nov-Dec;36(11-12):747-54. doi: 10.1055/s-2004-826158.
Results Reference
background
PubMed Identifier
12183643
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. doi: 10.1124/jpet.102.037481.
Results Reference
background
PubMed Identifier
15883751
Citation
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. doi: 10.1007/s10557-005-6892-4. No abstract available.
Results Reference
background
PubMed Identifier
24400077
Citation
Gejl M, Lerche S, Mengel A, Moller N, Bibby BM, Smidt K, Brock B, Sondergaard H, Botker 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.
Results Reference
derived

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

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