Clinical trial NCT00673595: Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo
Official title: Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Smoking
Keywords: smoking
varenicline
flow-mediated dilation
blood pressure
baroreflex
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2008-05-07
Enrollment: 19
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Arterial Endothelial Function as Measured by Flow-mediated Dilation
timeFrame: 2 weeks after participants quit smoking (study visit 3, day 15)
Secondary outcomes:
measure: 24-hour Ambulatory Blood Pressure
timeFrame: 2 weeks after participants quit smoking (study visit 3, day 15)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: John H Eisenach, M.D.
role: PRINCIPAL_INVESTIGATOR
References: