Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo

Not Applicable

Terminated

Conditions: Smoking

Interventions: Drug: Placebo
Drug: Varenicline

Registration Number: NCT00673595

Lead Sponsor: Mayo Clinic

Brief Summary: The purpose of this study is to evaluate endothelial function and autonomic regulation (for example, heart rate and blood pressure) in smokers before and after short-term smoking cessation. The endothelium is the thin layer of cells that lines the interior surface of blood vessels. The endothelium releases nitric oxide, which promotes dilation of the blood vessels and inhibits inflammation. Previous studies have shown that tobacco use is associated with endothelial dysfunction, and tobacco use increases heart rate and blood pressure.

We hypothesize that 2 weeks of smoking cessation will improve endothelial function. We will also determine if endothelial function and autonomic regulation after short-term smoking cessation differs for patients that achieve abstinence with the smoking cessation agent varenicline compared to placebo.

Detailed Description: Smoking is a major cardiovascular risk factor and is associated with arterial endothelial dysfunction, a key event in atherosclerosis. Previous observations have suggested that smoking-related endothelial dysfunction is dose-related and potentially reversible after withdrawal from smoking. To our knowledge, no data are available regarding potential improvement of arterial endothelial function in the first weeks of smoking cessation. This time frame is especially important because due to smoke-free policies in healthcare facilities, all smokers requiring surgery are abstinent from tobacco for at least some period of time.

Varenicline, a partial agonist at α4β2 neuronal nicotinic acetyl-choline (nAChR) receptors, received FDA approval as a novel medication for helping cigarette smokers to stop smoking. Given the anticipated common use of varenicline, it is important to define if the drug alters endothelial function and/or autonomic effects. Based on the lesser potency of varenicline (compared to nicotine) at nAChR receptors in peripheral ganglia and on endothelial cells of blood vessels, it may be hypothesized that varenicline has less or no influence on autonomic control of blood pressure and heart rate, and less or no influence on endothelial function.

Therefore, the aims of this study are 1) to determine the effects of short-term smoking cessation on endothelial function and autonomic regulation, and 2) to determine if these effects will be altered during treatment with varenicline.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 19

Inclusion Criteria

Regular smokers (currently >10 cigarettes/day; >5 pack years)
Willing to quit smoking for at least the duration of the study
Able and willing to give written informed consent

Exclusion Criteria

Known condition causing endothelial dysfunction except smoking (i.e. diabetes, hyperlipi¬demia, arterial hypertension, obesity)
Regular drug treatment and/or sporadic consumption of drugs within the last 4 weeks (exclusion has to be decided in each individual)
Acute or chronic illness
Participation in clinical trial within 1 month before the study
Excessive daily intake of alcohol (>2 servings per day) or caffeine (>4 servings/day)
Drug and/or alcohol abuse.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants on this arm will receive placebo tablets for 15 days.
Varenicline	Varenicline	Participants on this arm will receive varenicline tablets for 15 days.

Primary Outcome Measures

Name	Time	Method
Arterial Endothelial Function as Measured by Flow-mediated Dilation	2 weeks after participants quit smoking (study visit 3, day 15)	Flow-mediated dilation of the brachial artery will be measured using high-resolution ultrasound. Arterial diameter will be measured above the small cavity in the elbow joint from ultrasound images at rest in response to an increase in blood flow to the area. This blood flow will be induced by inflation of a blood pressure cuff placed around the forearm to a pressure of at least 50 mm Hg above systolic pressure for 5 min, followed by release. The ultrasound image of the artery will be recorded continuously from 30 sec before until 2 min after cuff release.

Secondary Outcome Measures

Name	Time	Method
24-hour Ambulatory Blood Pressure	2 weeks after participants quit smoking (study visit 3, day 15)	Ambulatory blood pressure will be measured using the Spacelabs 90202 recorder. Systolic and diastolic blood pressure during the 24-hour period will be analyzed.