SmokingNCT00673595
Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo
A study testing Varenicline in people with Smoking, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Smoking
- What is being tested?
- Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Feb 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Varenicline, Placebo
- Keywords
- smoking, varenicline, flow-mediated dilation, blood pressure, baroreflex
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called Chantix
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.
PlaceboDrug
The pharmacy will prepare tablets that match the varenicline tablets. The tablets should be taken orally after food intake with 200 ml of water.
| Study group | Role | What they receive |
|---|---|---|
| Varenicline | Active comparator | Participants on this arm will receive varenicline tablets for 15 days. Receives: Drug: Varenicline |
| Placebo | Placebo comparator | Participants on this arm will receive placebo tablets for 15 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial Endothelial Function as Measured by Flow-mediated Dilation
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.
Measured: 2 weeks after participants quit smoking (study visit 3, day 15)
Secondary outcomes (1)
24-hour Ambulatory Blood Pressure
Ambulatory blood pressure will be measured using the Spacelabs 90202 recorder. Systolic and diastolic blood pressure during the 24-hour period will be analyzed.
Measured: 2 weeks after participants quit smoking (study visit 3, day 15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study startMar 2007
- Primary completionFeb 2009
- Study completionFeb 2010
Why it stopped: Difficulty with recruiting sujects and subjects complying with the protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SmokingStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Investigators
- John H Eisenach, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00673595
- Sponsor's protocol ID
- 06-007194
- Status last verified
- Feb 2012
- First submitted
- 5 May 2008
- Last updated
- 16 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Function and Autonomic Regulation After Short-term Smoking Cessation: Varenicline Versus Placebo
- ClinicalTrials.gov ID
- NCT00673595
- Acronym / sponsor ID
- 06-007194
- Conditions
- Smoking
- Keywords
- smoking, varenicline, flow-mediated dilation, blood pressure, baroreflex
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty with recruiting sujects and subjects complying with the protocol
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 7 May 2008 (estimated)
- Results
- Posted 16 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline | Active comparator | Drug: VareniclineParticipants on this arm will receive varenicline tablets for 15 days. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants on this arm will receive placebo tablets for 15 days. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VareniclineAlso: ChantixSmoking 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. | Drug | Varenicline |
| PlaceboThe pharmacy will prepare tablets that match the varenicline tablets. The tablets should be taken orally after food intake with 200 ml of water. | Drug | Placebo |
Primary outcome
Arterial Endothelial Function as Measured by Flow-mediated Dilation
Time frame: 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.
1 secondary outcome
24-hour Ambulatory Blood Pressure
Time frame: 2 weeks after participants quit smoking (study visit 3, day 15)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John H Eisenach, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Varenicline in people with Smoking, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arterial Endothelial Function as Measured by Flow-mediated Dilation (time frame: 2 weeks after participants quit smoking (study visit 3, day 15)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2012.