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
  Purpose

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 Unpublished studies do however indicate that the improvement in the cardiovascular system is largely dependent upon a high blood glucose level and only partially dependent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 Intervention
Type 2 Diabetes Mellitus
Drug: Glucagon like peptide-1
Drug: Adenosine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Endothelial and Metabolic Effects of GLP-1 in Coronary Circulation in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • 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 ]

Enrollment: 35
Study Start Date: June 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

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
Study First Received: June 17, 2009
Last Updated: September 17, 2012
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: National Board of Health

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

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on September 22, 2014