Measuring Smoking Behaviors While Using Varenicline

Study Overview
=================
Brief Summary
-----------------
This study will demonstrate the behavioral responses to varenicline, helping to better understand its mechanisms. Hypotheses for the study are to observe decreases in smoking topography and nicotine cigarette choice on varenicline, relative to placebo; and decreases on day 21 relative to day 7 during varenicline treatment. We also propose to examine if extended duration of treatment has clinical significance in decreasing smoking behaviors, thus increasing the efficacy of varenicline.

Detailed Description
-----------------
This study is designed to examine the behavioral responses a cigarette smoker may have to using varenicline. Behavioral responses may help to better understand its mechanisms which in turn could improve treatment outcomes. The primary hypothesis for the study is to observe decreases in smoking topography, an objective measure of smoking behavior or puffing, on varenicline, relative to placebo; and decreases on day 21 relative to day 7 during varenicline treatment. We will also examine puffing and nicotine cigarette choices during lab visits at baseline, and Days 7 and 21. We also propose to examine if extended duration of treatment has clinical significance in decreasing smoking behaviors, thus potentially increasing the efficacy of varenicline.

Official Title
-----------------
Assessment of Smoking Topography and Behaviors During Response to Varenicline

Conditions
-----------------
Nicotine Dependence

Intervention / Treatment
-----------------
* Drug: Varenicline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: self report minimum 10 daily cigarettes self report smoking every day past 5 years between the ages 21-65 self report intention to try to quit smoking in the next 6 months Exclusion Criteria: self reported use of any nicotine-containing products other than non-menthol cigarettes self reported history or current treatment of substance abuse (other than nicotine dependence) self reported alcohol use greater than 25 standard drinks per week; currently pregnant, planned pregnancy or lactating (females: negative urine pregnancy screen) self reported history or current diagnosis of any Axis 1 disorders except past depression self reported serious or unstable disease within past year self reported history of epilepsy or seizure disorder; self reported history or current diagnosis of COPD (chronic obstructive pulmonary disease), cardiovascular disease, heart attack, or uncontrolled hypertension self reported kidney function impairment any current or recent (30 day) use of: smoking cessation medications, anti-psychotics, anti-depressants, anti-anxiety, panic medications, stimulants or opiate-containing medications less than 5 years of daily smoking any medical condition or concomitant medication that could compromise participant safety or treatment provide a baseline carbon monoxide (CO) reading < 10 ppm self reported use of non filtered cigarettes inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline before placebo<br>Drug (Varenicline (Chantix)): Placebo Intervention to be administered is: participants will receive standard dosing regimen of Varenicline for 21 days total, followed by 14-day washout and 21 days of placebo. Standard dosing: 0.5 mg days 1-3; 0.5 mg bid days 4-7; 1.0 mg bid days 8-21. | Drug: Varenicline<br>* Intervention Drug (Varenicline (Chantix) will be administered in standard dosing in pill format: 0.5 mg days 1-3; 0.5 mg bid daily days 4-7; 1.0 mg bid daily days 8-21.<br>* Other names: Chantix;|
| Experimental: Placebo then Varenicline<br>Placebo: Drug Varenicline (Chantix) Intervention to be administered is: participants will receive 21 days of placebo, followed by 14-day washout and standard dosing regimen of Varenicline for 21 days total. Standard dosing: 0.5 mg days 1-3; 0.5 mg bid days 4-7; 1.0 mg bid days 8-21. Intervention 'Drug (Varenicline (Chantix)): Placebo' | Drug: Varenicline<br>* Intervention Drug (Varenicline (Chantix) will be administered in standard dosing in pill format: 0.5 mg days 1-3; 0.5 mg bid daily days 4-7; 1.0 mg bid daily days 8-21.<br>* Other names: Chantix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Topography: Total Puff Volume | Total puff volume was created by summing all of the puffs from the cigarette smoked in the lab at each time point (each lab visit). This value represents the total volume of smoke extracted from a single cigarette and it a standard measure of smoking behavior. A total puff volume represents the total smoking volume from a cigarette. Values are reported in milliliters. Value of interest is the average puff volume across all sessions for all participants in a group and is reported as a key measure of smoking behavior. Analyses were repeated measures analysis of variance where individual, time and drug were within factors. | Days 1-21 of each of 2 study periods | 
| The Number of Choices of a Nicotine Containing Cigarette Compared to a Non-nicotine Cigarette. | Participants were given 4 puff choices (between a nicotine containing and de-nicotinized cigarette) on 6 study visits, for a total of 24 choices. Number of puffs reported is average across both study periods. | Days 1, 7, 21 of each of two 21 day study periods | 
| Daily Cigarette Consumption | Average of the number of cigarettes smoked per day | Two 21 day study periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Nicotine Metabolites From Urine Samples | Total urinary metabolites from urine samples collected at Day 1 and Day 21 | Samples from Day 1 and Day 21 of two 21 day Periods | 
| Nicotine Levels From Urine Samples | Nicotine levels from urine samples collected at Day 1 and Day 21. | Samples from Day 1 and Day 21 of two 21 day Periods | 
| Cotinine Levels From Urine Samples | Cotinine levels from urine samples collected at Day 1 and Day 21. | Samples from Day 1 and Day 21 of two 21 day Periods | 
| Carbon Monoxide Levels | Exhaled breath carbon monoxide levels collected at Day 1 and Day 21 sessions. Alveolar carbon monoxide is a validated assessment of smoke exposure. | Samples from Day 1 and Day 21 of two 21 day Periods | 
| Subjective Measures to Assess Smoking Urges | Craving for cigarettes was assessed with the 32-item Questionnaire of Smoking Urges (QSU) during each study visit. In order to calculate the QSU measure, each item is rated on a Likert-type scale from 1 (strongly disagree) to 7 (strongly agree). The values are then summed to create a single total score. Well validated 2 factor subscale scores were also created by summing the item scores for the 2 factors: Factor 1 reflects the desire to smoke for pleasure and Factor 2 reflects urges to smoke to relieve withdrawal-related negative affect. Internal consistency for each scale across all time points was high (Cronbach's α > 0.95, 0.85, and 0.95 for Factor 1, Factor 2, and QSU total, respectively). Scale range is 1-7 where 1 is low urge to smoke and 7 represents high urge to smoke. Data was collected at each time point but outcome measure of interest is end of period. | Days 21 of each of the two 21-day study periods, range 1(low)-7(high) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
smoking, nicotine, varenicline