Effect of Smoking Reduction on Endothelial Glucocalyx and Vascular Function

Study Overview
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Brief Summary
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The integrity of endothelial glucocalyx plays a vital role in vascular permeability and inflammation. Smoking cessation is related with improved vascular function and is a key component of secondary cardiovascular prevention. Pharmacotherapy is a standard component of evidence based smoking cessation treatment. This study was designed to determine the effects medically-aided smoking cessation on glucocalyx thickness and arterial elasticity smoking cessation programs

Detailed Description
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The investigators will examine smokers without cardiovascular disease treated with transdermal nicotine patches and/or varenicline at before, 4, 12, 24 and 48 weeks after treatment during validated smoking cessation program. The investigators will measure changes between baseline and 4,12,24, and 48 weeks after treatment of : exhaled carbon monoxide (CO, ppm) and self-reported number of cigarretes/day carotid-femoral pulse wave velocity (PWVc m/sec-Complior SP ALAM) and augmentation index (AI %-Arteriograph,TensioMed) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck). The PBR in microvessels is the cell-poor layer which results from the phase separation between the flowing red blood cells (RBC) and plasma. The PBR includes the most luminal part of glycocalyx that does allow cell penetration. Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a for deeper penetration of the RBC in the glucocalyx oxidative stress, thrombosis and inflammatory biomarkers in blood samples. Non smokers of similar age and sex will serve as controls.

Official Title
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Effect of Smoking Reduction on Endothelial Glucocalyx and Arterial Wall Properites During Medically-aided Smoking Cessation Program.

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Varenicline
* Drug: nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smokers Exclusion Criteria: Coronary artery disease Heart failure Diabetes mellitus Dyslipidemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: varenicline<br>Stimulation of nicotinic receptors by varenicline (Champix) 1,0 mg po | Drug: Varenicline<br>* Stimulation of nicotinic receptors by varenicline (Champix) 1,0 mg po<br>* Other names: Champix (varenicline);|
| Active Comparator: nicotine<br>Nicotine replacement therapy with transdermal patches and/or chewing gums | Drug: nicotine<br>* Nicotine replacement therapy with transdermal patches and/or chewing gums<br>* Other names: Nicorette (nicotine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in endothelial function between baseline and during medically-aided smoking cessation program. | Changes in endothelial function between baseline and during medically-aided smoking cessation program as assessed by endothelial glycocalyx thickness. | Baseline, 1 month, 3 months, 6 months and 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in a composite of markers of vascular function between baseline and during medically-aided smoking cessation program. | Changes in vascular function between baseline and during medically-aided as assessed by a composite of pulse wave velocity, augmentation index and central aortic blood pressure. | Baseline, 1 month, 3 months, 6 months and 12 months. | 
| Follow up for cardiovascular events | Association of endothelial glycocalyx as assessed by perfused boundary region (μm) with adverse cardiac events (composite of death, myocardial infarction, stroke , hospitalization for heart failure) during ten year follow -up in smokers and non-smoker subjects | baseline , ten years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arterial stiffness, Endothelial Glycocalyx