Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus
Primary Purpose
Type 2 Diabetes Mellitus, Coronary Artery Disease
Status
Completed
Phase
Not Applicable
Locations
Greece
Study Type
Interventional
Intervention
Liraglutide
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Arterial stiffness, Endothelial glycocalyx, Coronary flow reserve
Eligibility Criteria
Inclusion Criteria:
- Patients with type 2 diabetes mellitus (T2DM) without coronary artery disease (CAD)
- Patients with T2DM and CAD.
- Obese patients (BMI >30 Kg/m²) with abnormal oral glucose tolerance test (OGTT)
Exclusion Criteria:
- valvular heart disease
- congestive heart failure
- peripheral vascular disease
- liver or kidney failure
- history of alcohol or drug abuse
Sites / Locations
- ''Attikon'' University General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
liraglutide
Metformin
Arm Description
Outcomes
Primary Outcome Measures
Differences in Pulse Wave Velocity at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Differences in carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Differences in Augmentation Index at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Differences in augmentation index (AI, %) using oscillometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Differences in Coronary Flow Reserve at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Differences in coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Differences in Endothelial Glycocalyx Thickness at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. High PBR values represent reduced glycocalyx thickness.
Secondary Outcome Measures
Endothelial Glycocalyx and Pulse Wave Velocity.
Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Endothelial Glycocalyx and Coronary Flow Reserve.
Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03010683
Brief Title
Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus
Official Title
Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Athens
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Arterial stiffness is associated with increased risk for cardiovascular disease. Moreover, the integrity of endothelial glycocalyx plays a vital role in vascular permeability, inflammation and elasticity. Agonists of Glucagon like peptide - 1 receptors (GLP-1R) used in the treatment of type 2 diabetes mellitus (T2DM). This category includes exenatide and liraglutide. These drugs lower glucose levels by inhibiting the secretion of glucagon, promoting the release of insulin in response to hyperglycemia, slowing gastric emptying, and augmenting satiety. Clinical studies have shown that GLP-1R agonists have beneficial effects on cardiovascular function in both diabetic patients and healthy subjects. The purpose of this study is to investigate in patients with T2DM without coronary artery disease (CAD), patients with T2DM and CAD and obese patients with abnormal oral glucose tolerance test (OGTT), changes in arterial stiffness, endothelial glycocalyx thickness and coronary reserve flow (CFR) after treatment with metformin or agonist GLP-1R.
Detailed Description
The investigators will study three groups matched for age and sex: 30 patients with type 2 diabetes mellitus (T2DM) without coronary artery disease (CAD), 30 patients with T2DM and CAD and 30 obese patients (BMI >30 Kg/m²) with abnormal oral glucose tolerance test (OGTT). It will be a randomized study with metformin or GLP-1R agonist treatment for 1 year. All subjects will receive for 1 year: (a) GLP-1R agonist or (b) metformin. At 0, 3, 6 and 12 months, where 0 is the starting point of treatment, blood samples will be collected.
At 0, 3, 6 and 12 months the investigators will measure:
Carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry by Complior (SP ALAM) and augmentation index (AI, %) by the method of arteriography (Arteriograph, TensioMed)
Perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate non invasive index of reduced endothelial glucocalyx thickness.
Coronary flow reserve (CFR) in the left anterior descending artery after infusion of adenosine using Doppler echocardiography.
Determination of the following parameters in blood: glucose, insulin, free fatty acids, triglycerides, glycerol, C reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated Phospholipase A2 (LP-LPA2), tumor necrosis factor-a (TNF-a), interleukins 6 and 10 (IL6 and IL10), propeptide of type I procollagen (PIP), propeptide of procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP), macrophage-colony stimulating factor (MCSF), growth differentiation factor-15 (GDF-15), N-terminal pro b-type natriuretic peptide (NT-proBNP) and galectin-3.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, Coronary Artery Disease
Keywords
Arterial stiffness, Endothelial glycocalyx, Coronary flow reserve
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
liraglutide
Arm Type
Active Comparator
Arm Title
Metformin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Victoza (liraglutide)
Intervention Description
Stimulation of Glucagon like peptide-1 receptor by liraglutide (Victoza) 1.8mg once daily as a subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage (Metformin)
Intervention Description
Antidiabetic drug-biguanide class (Glucophage) 1000mg twice daily per os
Primary Outcome Measure Information:
Title
Differences in Pulse Wave Velocity at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Description
Differences in carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Time Frame
Baseline, 3 months, 6 months and 12 months
Title
Differences in Augmentation Index at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Description
Differences in augmentation index (AI, %) using oscillometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Time Frame
Baseline, 3 months, 6 months, and 12 months.
Title
Differences in Coronary Flow Reserve at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Description
Differences in coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Time Frame
Baseline, 3 months, 6 months, and 12 months.
Title
Differences in Endothelial Glycocalyx Thickness at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.
Description
Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. High PBR values represent reduced glycocalyx thickness.
Time Frame
Baseline, 3 months, 6 months, and 12 months.
Secondary Outcome Measure Information:
Title
Endothelial Glycocalyx and Pulse Wave Velocity.
Description
Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Time Frame
Baseline, 3 months, 6 months, and 12 months.
Title
Endothelial Glycocalyx and Coronary Flow Reserve.
Description
Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.
Time Frame
Baseline, 3 months, 6 months, and 12 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patients with type 2 diabetes mellitus (T2DM) without coronary artery disease (CAD)
Patients with T2DM and CAD.
Obese patients (BMI >30 Kg/m²) with abnormal oral glucose tolerance test (OGTT)
Exclusion Criteria:
valvular heart disease
congestive heart failure
peripheral vascular disease
liver or kidney failure
history of alcohol or drug abuse
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ignatios Ikonomidis, MD
Organizational Affiliation
2nd Cardiology Department, University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
George Pavlidis, MD
Organizational Affiliation
2nd Cardiology Department, University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vaia Lambadiari, MD
Organizational Affiliation
2nd Department of Internal Medicine, University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fotini Kousathana, MD
Organizational Affiliation
2nd Department of Internal Medicine, University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
George Dimitriadis, MD
Organizational Affiliation
2nd Department of Internal Medicine, University of Athens, Greece
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Lekakis, MD
Organizational Affiliation
2nd Cardiology Department, University of Athens, Greece
Official's Role
Principal Investigator
Facility Information:
Facility Name
''Attikon'' University General Hospital
City
Athens
State/Province
Attiki
ZIP/Postal Code
12462
Country
Greece
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32501595
Citation
Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.
Results Reference
derived
PubMed Identifier
29310645
Citation
Lambadiari V, Pavlidis G, Kousathana F, Varoudi M, Vlastos D, Maratou E, Georgiou D, Andreadou I, Parissis J, Triantafyllidi H, Lekakis J, Iliodromitis E, Dimitriadis G, Ikonomidis I. Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes. Cardiovasc Diabetol. 2018 Jan 8;17(1):8. doi: 10.1186/s12933-017-0646-z.
Results Reference
derived
Learn more about this trial
Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus
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