ClinicalTrials.gov
ClinicalTrials.gov Menu

Endothelial and Metabolic Effects of Glucagon-like Peptide-1 (GLP-1) in Coronary Circulation in Patients With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00923962
Recruitment Status : Completed
First Posted : June 18, 2009
Last Update Posted : September 18, 2012
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Jacob Christian Sivertsen, University Hospital, Gentofte, Copenhagen

Study Description
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

GLP-1 is an incretin hormone which is discharged from the intestines after food intake. The hormone is known for its powerful insulinotropic and trophic effects on the beta cells in the pancreas and is currently used as an anti-diabetic agent in patients with type 2 diabetes (T2DM).

GLP-1 receptors are widely distributed including on the endothelial cells in both coronary and skeletal muscle circulation and on the myocardium. GLP-1-receptor studies on knock-out mice have shown that they exhibit a reduced myocardial contractility and reduced diastolic heart function. GLP-1 also shows beneficial cardiovascular effects in patients with acute myocardial infarctions and dogs with dilated cardiomyopathy in that the left ventricle function and endothelial dysfunction improves after GLP-1 treatment via insulin-independent mechanisms. Preclinical studies indicate that exogenous administrated GLP-1 in physiological concentrations can improve perfusion but this has never been tested in humans. It is also unknown whether GLP-1 can directly increase the glucose/metabolite uptake across both cardiac and skeletal muscle in an insulin independent manner. Unpublished studies do however indicate that the improvement in the cardiovascular system is largely dependent upon a high blood glucose level and only partially dependent upon the antiglycemic effects of GLP-1.

In the proposed studies the investigators wish to examine the physiological role of GLP-1 receptor stimulation both with regard to perfusion, metabolic improvement as well as cardiac inotropic. These studies will be conducted in both healthy and in T2DM patients.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Glucagon like peptide-1 Drug: Adenosine Not Applicable

Study Design
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: Endothelial and Metabolic Effects of GLP-1 in Coronary Circulation in Patients With Type 2 Diabetes Mellitus
Study Start Date : June 2009
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Type 2 Diabetes patients Drug: Glucagon like peptide-1
0,1 pmol/kg/min
Drug: Adenosine
20-40 microgram/minute
Active Comparator: Healthy Drug: Glucagon like peptide-1
0,1 pmol/kg/min
Drug: Adenosine
20-40 microgram/minute
Active Comparator: Artherosclerosis Drug: Glucagon like peptide-1
0,1 pmol/kg/min
Drug: Adenosine
20-40 microgram/minute


Outcome Measures
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Coronary blood flow [ Time Frame: 10 minutes after I.A. GLP-1 ]
  2. Coronary metabolite uptake [ Time Frame: 10 minutes after I.A. GLP-1 ]

Eligibility Criteria
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Caucasians over 18
  • Emitted for non-acute coronary arteriography (CAG) in Gentofte hospital
  • BMI 23-35 kg/m2
  • Normal hemoglobin
  • Who gives informed consent
  • Those with type 2 diabetes: HbA1c 6-10%
  • Those without type 2 diabetes: Normal oral glucose tolerance test (OGTT) according to WHO criteria

Exclusion Criteria:

  • Liver disease (ALAT > 2x normal)
  • Diabetic nefropati (Creatinine > 130 µM or albuminuria)
  • Treatment with medicine that cannot be paused 12 hours before intervention
  • Pregnancy or breastfeeding
  • Insulin- or glitazone treatment
  • Healthy controls: close family history with diabetes
  • Unstable angina pectoris
  • Non-STEMI
  • Atrial fibrillation
  • Valvular disease
  • LVEF < 50%
  • Severe systemic disease
  • Type 1 diabetes
Contacts and Locations
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00923962


Locations
Denmark
University Hospital Gentofte, Department of Cardiology
Gentofte, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Jan S Jensen, MD, DMSc University hospital Gentofte, Department of Cardiology
Principal Investigator: Jaya Rosenmeier, MD, Ph.D. University hospital Gentofte, Department of Cardiology
More Information
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Responsible Party: Jacob Christian Sivertsen, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT00923962     History of Changes
Other Study ID Numbers: GLP-1 Coronary circulation 01
First Posted: June 18, 2009    Key Record Dates
Last Update Posted: September 18, 2012
Last Verified: September 2012

Keywords provided by Jacob Christian Sivertsen, University Hospital, Gentofte, Copenhagen:
Basic science
Type 2 Diabetes mellitus
Glucagon like peptid-1
Coronary Bloodflow
Metabolite uptake

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Glucagon-Like Peptide 1
Adenosine
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
 Incretins
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action