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

NCT ID: NCT00673595

Last Updated: 2012-03-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-02-28

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.

Conditions

Smoking

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Varenicline

Participants on this arm will receive varenicline tablets for 15 days.

Group Type: ACTIVE_COMPARATOR

Varenicline

Intervention Type: DRUG

Smoking cessation assistance: study days 1-3: 0.5 mg once daily, study days 4-7: 0.5 mg twice daily, study days 8-15: 1 mg twice daily; study day 16: 1 mg once. The tablets should be taken orally after food intake with 200 ml of water.

The treatment phase may be prolonged up to a maximum of 2 weeks under the following conditions: 1) the participant voluntarily agrees to the prolongation of the study, 2) both the participant and investigator are confident that the participant will be able to completely refrain from smoking for at least 10 days until the final study day.

Placebo

Participants on this arm will receive placebo tablets for 15 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The pharmacy will prepare tablets that match the varenicline tablets. The tablets should be taken orally after food intake with 200 ml of water.

Interventions

Varenicline

Smoking cessation assistance: study days 1-3: 0.5 mg once daily, study days 4-7: 0.5 mg twice daily, study days 8-15: 1 mg twice daily; study day 16: 1 mg once. The tablets should be taken orally after food intake with 200 ml of water.

The treatment phase may be prolonged up to a maximum of 2 weeks under the following conditions: 1) the participant voluntarily agrees to the prolongation of the study, 2) both the participant and investigator are confident that the participant will be able to completely refrain from smoking for at least 10 days until the final study day.

Intervention Type: DRUG

Placebo

The pharmacy will prepare tablets that match the varenicline tablets. The tablets should be taken orally after food intake with 200 ml of water.

Intervention Type: DRUG

Other Intervention Names

Chantix

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

John H Eisenach, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

06-007194

Identifier Type: -

Identifier Source: org_study_id