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

This study has been terminated.
(Difficulty with recruiting sujects and subjects complying with the protocol)
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00673595
First received: May 5, 2008
Last updated: February 21, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention
Smoking
Drug: Varenicline
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Arterial Endothelial Function as Measured by Flow-mediated Dilation [ Time Frame: 2 weeks after participants quit smoking (study visit 3, day 15) ] [ Designated as safety issue: No ]
    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:
  • 24-hour Ambulatory Blood Pressure [ Time Frame: 2 weeks after participants quit smoking (study visit 3, day 15) ] [ Designated as safety issue: No ]
    Ambulatory blood pressure will be measured using the Spacelabs 90202 recorder. Systolic and diastolic blood pressure during the 24-hour period will be analyzed.


Enrollment: 19
Study Start Date: March 2007
Study Completion Date: February 2010
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Varenicline
Participants on this arm will receive varenicline tablets for 15 days.
Drug: 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.

Other Name: Chantix
Placebo Comparator: Placebo
Participants on this arm will receive placebo tablets for 15 days.
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.

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

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673595

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: John H Eisenach, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: John H. Eisenach, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00673595     History of Changes
Other Study ID Numbers: 06-007194
Study First Received: May 5, 2008
Results First Received: February 21, 2012
Last Updated: February 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
smoking
varenicline
flow-mediated dilation
blood pressure
baroreflex

Additional relevant MeSH terms:
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014