Trial Outcomes & Findings for Varenicline and Nicotine Interactions in Humans (VA) (NCT NCT00606892)

Last Updated: 2014-09-25

Results Overview

The Drug Effects Questionaire( DEQ) is a 7-item psychometric that measures the following subjective categories: 'drug strength',' high', 'feels stimulated', 'good effects', 'bad effects', 'head rush', and 'like the drug'. Smokers rated each item on a 100 millimeter scale from "not at all" (a score of 0) to "extremely" with a maximum score of 100.

Recruitment status

COMPLETED

Study phase

Target enrollment

37 participants

Primary outcome timeframe

30 minutes after each nicotine infusion

Results posted on

2014-09-25

Participant Flow

Subjects were recruited from the New Haven Connecticut area through newspaper advertisements and fliers from the summer of 2007 thru the winter of 2008.

There was no special pre-assignment procedures for this study. Thirty seven smokers signed a consent form with only 17 randomized. 13 smokers never return to clinic after signing a consent form. 2 smokers were excluded secondary to poor IV access. 5 smokers had dropped out due to a scheduling conflict.

Participant milestones

Participant milestones
Measure	Placebo First, Then Varenicline Subject received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg). After a minimum washout period of 5 days,then subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg).	Varenicline First, Then Placebo Subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg).After a minimum of washout period of 5 days, then subjects received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg).
Adaptation STARTED	9	8
Adaptation COMPLETED	9	8
Adaptation NOT COMPLETED	0	0
First Intervention STARTED	9	8
First Intervention COMPLETED	8	4
First Intervention NOT COMPLETED	1	4
Washout Period STARTED	8	4
Washout Period COMPLETED	8	4
Washout Period NOT COMPLETED	0	0
Second Intervention STARTED	8	4
Second Intervention COMPLETED	8	4
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo First, Then Varenicline Subject received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg). After a minimum washout period of 5 days,then subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg).	Varenicline First, Then Placebo Subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg).After a minimum of washout period of 5 days, then subjects received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg).
First Intervention Protocol Violation	1	4

Baseline Characteristics

Varenicline and Nicotine Interactions in Humans (VA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=12 Participants Includes all subjects who completed the study. (The total number of subjects who were enrolled in both arms of the study.)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	34.0 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes after each nicotine infusion

Population: All participants who complete all interventions.

Outcome measures

Outcome measures
Measure	Placebo, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and prior to the nicotine infusions.	Placebo, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and 30 minutes after the nicotine infusions.	Varenicline, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition prior to the nicotine infusions.	Varenicline, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition and 30 minutes after the nicotine infusions.	Varenicline/ Medium Dose Nicotine n=12 Participants The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the medium dose (0.4) of IV nicotine under the varenicline condition.	Varenicline/ High Dose Nicotine n=12 Participants The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the high dose (0.7) of IV nicotine under the varenicline condition.
Subjective Responses to Intravenous Nicotine High	23 millimeters Standard Error 8	38 millimeters Standard Error 10	51 millimeters Standard Error 10	14 millimeters Standard Error 4	27 millimeters Standard Error 7	37 millimeters Standard Error 8
Subjective Responses to Intravenous Nicotine Bad Effects	7 millimeters Standard Error 3	15 millimeters Standard Error 7	23 millimeters Standard Error 8	8 millimeters Standard Error 3	8 millimeters Standard Error 3	20 millimeters Standard Error 8
Subjective Responses to Intravenous Nicotine Like the Drug	18 millimeters Standard Error 8	27 millimeters Standard Error 9	35 millimeters Standard Error 10	14 millimeters Standard Error 4	25 millimeters Standard Error 8	35 millimeters Standard Error 9
Subjective Responses to Intravenous Nicotine Head Rush	24 millimeters Standard Error 8	40 millimeters Standard Error 9	51 millimeters Standard Error 9	11 millimeters Standard Error 4	28 millimeters Standard Error 7	37 millimeters Standard Error 8
Subjective Responses to Intravenous Nicotine Feels Stimulated	25 millimeters Standard Error 8	34 millimeters Standard Error 10	38 millimeters Standard Error 10	11 millimeters Standard Error 4	24 millimeters Standard Error 8	35 millimeters Standard Error 9
Subjective Responses to Intravenous Nicotine Drug Strength	24 millimeters Standard Error 8	41 millimeters Standard Error 9	58 millimeters Standard Error 09	16 millimeters Standard Error 4	32 millimeters Standard Error 7	40 millimeters Standard Error 8
Subjective Responses to Intravenous Nicotine Good Effects	19 millimeters Standard Error 8	30 millimeters Standard Error 8	45 millimeters Standard Error 10	22 millimeters Standard Error 8	25 millimeters Standard Error 8	34 millimeters Standard Error 9

SECONDARY outcome

Timeframe: pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine)

Population: Data from all subjects who completed both experimental sessions (nicotine infusion after 4 days of placebo and also 4 days of varneicline, n=12) are presented. RT's \< 100 ms, or \> 1501 ms were excluded from the analysis (\>3 SD's of the mean). The data presented are the mean RT's to identifying word colors under each treatment condition.

A Modified stroop task was used to assess attentional responses to smoking and negative affect cues. Cues were presented as blue, red or green text. Subjects completed 2 counterbalanced blocks (60 trials per block). One block contained smoking cues and neutral cues. The other block contained negative affect cues and a different set of matched neutral cues. The 2 blocks were administered twice during each experimental session - prior to nicotine infusion, and 30 mins after the last nicotine infusion (2 hrs and 45 mins after medication dosing). The Stroop effect is a differential RT when identifying the colors of words presented as neutral cues vs. emotional cues (i.e. smoking or negative affect cues).

Outcome measures

Outcome measures
Measure	Placebo, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and prior to the nicotine infusions.	Placebo, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and 30 minutes after the nicotine infusions.	Varenicline, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition prior to the nicotine infusions.	Varenicline, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition and 30 minutes after the nicotine infusions.	Varenicline/ Medium Dose Nicotine The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the medium dose (0.4) of IV nicotine under the varenicline condition.	Varenicline/ High Dose Nicotine The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the high dose (0.7) of IV nicotine under the varenicline condition.
Mean Reaction Time (RT) on Modified Stroop Task. Negative Affect block	679.0 milliseconds Standard Deviation 104.1	641.3 milliseconds Standard Deviation 114.9	665.8 milliseconds Standard Deviation 177.1	631.7 milliseconds Standard Deviation 128.6	—	—
Mean Reaction Time (RT) on Modified Stroop Task. Neutral Block- Negative Affect Cue	692.5 milliseconds Standard Deviation 117.5	661.5 milliseconds Standard Deviation 111.1	644.8 milliseconds Standard Deviation 122.8	618.6 milliseconds Standard Deviation 108.5	—	—
Mean Reaction Time (RT) on Modified Stroop Task. Smoking Block	722.3 milliseconds Standard Deviation 131.3	693.1 milliseconds Standard Deviation 129.4	660.1 milliseconds Standard Deviation 137.8	624.2 milliseconds Standard Deviation 100.1	—	—
Mean Reaction Time (RT) on Modified Stroop Task. Neutral Block- Smoking Cue	702.3 milliseconds Standard Deviation 148.6	686.7 milliseconds Standard Deviation 134.1	652.1 milliseconds Standard Deviation 115.5	618.6 milliseconds Standard Deviation 104.7	—	—

SECONDARY outcome

Timeframe: Before each laboratory session on day 5

Population: Subjects finishing the complete study. (n=12)

Subject Cotinine Levels before each laboratory session.

Outcome measures

Outcome measures
Measure	Placebo, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and prior to the nicotine infusions.	Placebo, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and 30 minutes after the nicotine infusions.	Varenicline, Pre-Nicotine Mean reaction time during modified Stroop task under the varenicline condition prior to the nicotine infusions.	Varenicline, Post-Nicotine Mean reaction time during modified Stroop task under the varenicline condition and 30 minutes after the nicotine infusions.	Varenicline/ Medium Dose Nicotine The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the medium dose (0.4) of IV nicotine under the varenicline condition.	Varenicline/ High Dose Nicotine The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the high dose (0.7) of IV nicotine under the varenicline condition.
Cotinine Levels	202 ng/mL Standard Deviation 41	185 ng/mL Standard Deviation 38	—	—	—	—

SECONDARY outcome

Timeframe: 30 minutes after each nicotine infusion

Population: Changes in heart rate, systolic and diastolic blood pressure during the experimental sessions were analyzed on all subjects who completed both experimental sessions (n=12).

The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated.

Outcome measures

Outcome measures
Measure	Placebo, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and prior to the nicotine infusions.	Placebo, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the placebo condition and 30 minutes after the nicotine infusions.	Varenicline, Pre-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition prior to the nicotine infusions.	Varenicline, Post-Nicotine n=12 Participants Mean reaction time during modified Stroop task under the varenicline condition and 30 minutes after the nicotine infusions.	Varenicline/ Medium Dose Nicotine n=12 Participants The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the medium dose (0.4) of IV nicotine under the varenicline condition.	Varenicline/ High Dose Nicotine n=12 Participants The average peak change (change score) in the subjective responses to the 7-items of the DEQ to the high dose (0.7) of IV nicotine under the varenicline condition.
Heart Rate	7 beats per minute Standard Error 1	13 beats per minute Standard Error 2	16 beats per minute Standard Error 2	2 beats per minute Standard Error 2	5 beats per minute Standard Error 1	5 beats per minute Standard Error 2

SECONDARY outcome

Timeframe: 30 minutes after each nicotine infusion

Population: Changes in heart rate, systolic and diastolic blood pressure during the experimental sessions were analyzed on all subjects who completed both experimental sessions (n=12).

The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion.