Effect of Smoking Reduction on Endothelial Glucocalyx and Vascular Function

• ClinicalTrials.gov Identifier: NCT02307045
• Recruitment Status: Unknown
• First Posted: December 3, 2014
• Last Update Posted: April 3, 2020
• Sponsor: University of Athens
• Information provided by (Responsible Party): Ignatios Ikonomidis, University of Athens

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Smoking Cessation	Drug: Varenicline; Drug: nicotine	Phase 4

Detailed Description:

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 :

1. exhaled carbon monoxide (CO, ppm) and self-reported number of cigarretes/day
2. carotid-femoral pulse wave velocity (PWVc m/sec-Complior SP ALAM) and augmentation index (AI %-Arteriograph,TensioMed)
3. 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
4. oxidative stress, thrombosis and inflammatory biomarkers in blood samples.

Non smokers of similar age and sex will serve as controls.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of Smoking Reduction on Endothelial Glucocalyx and Arterial Wall Properites During Medically-aided Smoking Cessation Program.
• Actual Study Start Date: December 3, 2014
• Estimated Primary Completion Date: November 30, 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: varenicline; Stimulation of nicotinic receptors by varenicline (Champix) 1,0 mg po	Drug: Varenicline; Stimulation of nicotinic receptors by varenicline (Champix) 1,0 mg po; Other Name: Champix (varenicline)
Active Comparator: nicotine; Nicotine replacement therapy with transdermal patches and/or chewing gums	Drug: nicotine; Nicotine replacement therapy with transdermal patches and/or chewing gums; Other Name: Nicorette (nicotine)

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Changes in a composite of markers of vascular function between baseline and during medically-aided smoking cessation program. [ Time Frame: Baseline, 1 month, 3 months, 6 months and 12 months. ]
   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.
2. Follow up for cardiovascular events [ Time Frame: baseline , ten years ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Smokers

Exclusion Criteria:

• Coronary artery disease
• Heart failure
• Diabetes mellitus
• Dyslipidemia

Contacts and Locations

Locations

Greece

''Attikon'' University General Hospital

Athens, Attiki, Greece, 12462

Sponsors and Collaborators

University of Athens

Investigators

• Principal Investigator: Ignatios Ikonomidis, MD; 2nd Cardiology Department, University of Athens, Greece
• Principal Investigator: Kalliroi Kourea, MD; 2nd Cardiology Department, University of Athens, Greece
• Principal Investigator: George Pavlidis, MD; 2nd Cardiology Department, University of Athens, Greece
• Principal Investigator: Margarita Marinou, MD; 2nd Cardiology Department, University of Athens, Greece
• Principal Investigator: John Lekakis, MD; 2nd Cardiology Department, University of Athens, Greece

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ikonomidis I, Marinou M, Vlastos D, Kourea K, Andreadou I, Liarakos N, Triantafyllidi H, Pavlidis G, Tsougos E, Parissis J, Lekakis J. Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program. Atherosclerosis. 2017 Jul;262:123-130. doi: 10.1016/j.atherosclerosis.2017.05.012. Epub 2017 May 13.

• Responsible Party: Ignatios Ikonomidis, Assistant Professor in Cardiology, University of Athens
• ClinicalTrials.gov Identifier: NCT02307045
• Other Study ID Numbers: SMOKING-VAR-NIC-ATTIKON
• First Posted: December 3, 2014
• Last Update Posted: April 3, 2020
• Last Verified: April 2020

Keywords provided by Ignatios Ikonomidis, University of Athens:

Arterial stiffness; Endothelial Glycocalyx

Additional relevant MeSH terms:

Nicotine; Varenicline; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action