Measuring Smoking Behaviors While Using Varenicline

Assessment of Smoking Topography and Behaviors During Response to Varenicline

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00948155

Enrollment

Registered

2009-07-29

Start date

2009-01-31

Completion date

2010-11-30

Last updated

2014-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nicotine Dependence

Keywords

smoking, nicotine, varenicline

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.

Interventions

DRUGVarenicline

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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Smoking Topography: Total Puff Volume	Days 1-21 of each of 2 study periods	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.
The Number of Choices of a Nicotine Containing Cigarette Compared to a Non-nicotine Cigarette.	Days 1, 7, 21 of each of two 21 day study periods	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.
Daily Cigarette Consumption	Two 21 day study periods	Average of the number of cigarettes smoked per day

Secondary

Measure	Time frame	Description
Carbon Monoxide Levels	Samples from Day 1 and Day 21 of two 21 day Periods	Exhaled breath carbon monoxide levels collected at Day 1 and Day 21 sessions. Alveolar carbon monoxide is a validated assessment of smoke exposure.
Total Nicotine Metabolites From Urine Samples	Samples from Day 1 and Day 21 of two 21 day Periods	Total urinary metabolites from urine samples collected at Day 1 and Day 21
Subjective Measures to Assess Smoking Urges	Days 21 of each of the two 21-day study periods, range 1(low)-7(high)	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.
Nicotine Levels From Urine Samples	Samples from Day 1 and Day 21 of two 21 day Periods	Nicotine levels from urine samples collected at Day 1 and Day 21.
Cotinine Levels From Urine Samples	Samples from Day 1 and Day 21 of two 21 day Periods	Cotinine levels from urine samples collected at Day 1 and Day 21.

Countries

United States

Participant flow

Recruitment details

Recruitment occurred in a research laboratory in a school of medicine. Dates of recruitment: first participant first visit March 31, 2009; last participants last visit December 02, 2010

Pre-assignment details

48 participants signed consents and were enrolled in the study. Medical clearance was achieved by 41; 29 returned for the first laboratory visit which is the first day drug/placebo was administered. The 12 who did not return for the Day 1 visit were not included further in the study. There was a minimum 14 washout period between drug conditions.

Participants by arm

Arm	Count
Placebo Then Varenicline 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. Varenicline (Chantix) : 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.	14
Varenicline Before Placebo 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. Varenicline (Chantix) : 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.	15
Total	29

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention 21 Days	Lost to Follow-up	2	2
Washout 14 Days	Lost to Follow-up	1	2

Baseline characteristics

Characteristic	Varenicline Before Placebo	Placebo Then Varenicline	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants	14 Participants	29 Participants
Age, Continuous	37.6 years STANDARD_DEVIATION 12.8	42.6 years STANDARD_DEVIATION 13.7	39.9 years STANDARD_DEVIATION 13.3
Region of Enrollment United States	15 participants	14 participants	29 participants
Sex: Female, Male Female	3 Participants	4 Participants	7 Participants
Sex: Female, Male Male	12 Participants	10 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 14	0 / 15
serious Total, serious adverse events	0 / 14	0 / 15

Outcome results

Primary

Daily Cigarette Consumption

Average of the number of cigarettes smoked per day

Time frame: Two 21 day study periods

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo Then Varenicline	Daily Cigarette Consumption	Start of 21 day period	16.2 number of cigarettes smoked per day	Standard Error 1.4
Placebo Then Varenicline	Daily Cigarette Consumption	End of 21 day period	14.4 number of cigarettes smoked per day	Standard Error 1.2
Varenicline Before Placebo	Daily Cigarette Consumption	End of 21 day period	12.8 number of cigarettes smoked per day	Standard Error 1.3
Varenicline Before Placebo	Daily Cigarette Consumption	Start of 21 day period	16.1 number of cigarettes smoked per day	Standard Error 0.86

Primary

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.

Time frame: Days 1-21 of each of 2 study periods

Population: All those participants who completed both study periods were included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo Then Varenicline	Smoking Topography: Total Puff Volume	523.4 milliliters	Standard Error 41
Varenicline Before Placebo	Smoking Topography: Total Puff Volume	684.6 milliliters	Standard Error 33

Primary

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.

Time frame: Days 1, 7, 21 of each of two 21 day study periods

Population: All participants who completed the task were included in the analysis

Arm	Measure	Value (MEAN)	Dispersion
Placebo Then Varenicline	The Number of Choices of a Nicotine Containing Cigarette Compared to a Non-nicotine Cigarette.	12 number of puffs chosen of a maximum 24	Standard Error 4.5
Varenicline Before Placebo	The Number of Choices of a Nicotine Containing Cigarette Compared to a Non-nicotine Cigarette.	11.5 number of puffs chosen of a maximum 24	Standard Error 5.1

Secondary

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.

Time frame: Samples from Day 1 and Day 21 of two 21 day Periods