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

Coronary Artery Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03010683
• Other study ID #: GLP1-DM-ATTIKON
• Status: Completed
• Phase: N/A
• Start date: November 2015
• Est. completion date: December 2017

Study information

• Verified date: March 2021
• Source: University of Athens
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. 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)

2. 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.

3. Coronary flow reserve (CFR) in the left anterior descending artery after infusion of adenosine using Doppler echocardiography.

4. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Liraglutide
Stimulation of Glucagon like peptide-1 receptor by liraglutide (Victoza) 1.8mg once daily as a subcutaneous injection
• Metformin
Antidiabetic drug-biguanide class (Glucophage) 1000mg twice daily per os

Locations

Country	Name	City	State
Greece	''Attikon'' University General Hospital	Athens	Attiki

Sponsors (1)

Lead Sponsor	Collaborator
University of Athens

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, 3 months, 6 months and 12 months
Primary	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.	Baseline, 3 months, 6 months, and 12 months.
Primary	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.	Baseline, 3 months, 6 months, and 12 months.
Primary	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.	Baseline, 3 months, 6 months, and 12 months.
Secondary	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.	Baseline, 3 months, 6 months, and 12 months.
Secondary	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.	Baseline, 3 months, 6 months, and 12 months.