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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Jacob Christian Sivertsen, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT00923962
First received: June 17, 2009
Last updated: September 17, 2012
Last verified: September 2012

June 17, 2009
September 17, 2012
June 2009
January 2012   (final data collection date for primary outcome measure)
  • Coronary blood flow [ Time Frame: 10 minutes after I.A. GLP-1 ] [ Designated as safety issue: No ]
  • Coronary metabolite uptake [ Time Frame: 10 minutes after I.A. GLP-1 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00923962 on ClinicalTrials.gov Archive Site
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Endothelial and Metabolic Effects of Glucagon-like Peptide-1 (GLP-1) in Coronary Circulation in Patients With Type 2 Diabetes Mellitus
Endothelial and Metabolic Effects of GLP-1 in Coronary Circulation in Patients With Type 2 Diabetes Mellitus

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 Unpublished studies do however indicate that the improvement in the cardiovascular system is largely dependent upon a high blood glucose level and only partially dependent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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Type 2 Diabetes Mellitus
  • Drug: Glucagon like peptide-1
    0,1 pmol/kg/min
  • Drug: Adenosine
    20-40 microgram/minute
  • Active Comparator: Type 2 Diabetes patients
    Interventions:
    • Drug: Glucagon like peptide-1
    • Drug: Adenosine
  • Active Comparator: Healthy
    Interventions:
    • Drug: Glucagon like peptide-1
    • Drug: Adenosine
  • Active Comparator: Artherosclerosis
    Interventions:
    • Drug: Glucagon like peptide-1
    • Drug: Adenosine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
January 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00923962
GLP-1 Coronary circulation 01
No
Jacob Christian Sivertsen, University Hospital, Gentofte, Copenhagen
University Hospital, Gentofte, Copenhagen
Merck Sharp & Dohme Corp.
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
University Hospital, Gentofte, Copenhagen
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP