Varenicline and Nicotine Interactions in Humans (VA)

Not Applicable

Completed

Conditions: Smoking Cessation

Interventions: Drug: Varenicline
Drug: Placebo
Drug: IV Nic

Registration Number: NCT00606892

Lead Sponsor: Yale University

Brief Summary: To examine the effects of varenicline on the subjective, physiological and cognitive responses to intravenous nicotine. Varenicline is a partial nicotine agonist and it is approved as a treatment for smoking cessation. We predict that varenicline treatment will modify subjective, physiological and cognitive responses to IV nicotine.

Detailed Description: This will be a 2-4 week double-blind, placebo-controlled study. Twenty four male and female smokers will have two 4-day treatment periods, in which they will be randomized to varenicline (1 mg/day) or placebo. During the first 3 days of each treatment period, smokers will have daily clinic visits and receive their study medication. On Day 4, subjects will come to the laboratory, where they will receive ascending doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg per 70kg). This procedure will allow accurate assessment of varenicline effects on the subjective, physiological and cognitive responses to nicotine. Following a washout period, subjects will be crossed over to the alternative treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Female and male smokers, aged 18 to 55 years
History of smoking daily for the past 12 months, at least 15 cigarettes daily
Carbon Monoxide (Alveolar) level > 10ppm
For women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods

Exclusion Criteria

History of heart disease, renal or hepatic diseases
other medical conditions that the physician investigator deems as contraindicated for the subject to be in the study
Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
recent psychiatric diagnosis and treatment for Axis I disorders including
major depression, bipolar affective disorder,
schizophrenia and panic disorder within the past year
Current dependence on alcohol
drugs or treatments for drug
alcohol addiction within the past 5 years
Allergy to varenicline

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Varenicline first, placebo, + IV Nic	Placebo	Subjects received Varenicline tablet (1 mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg). After a washout of a minimum of 5 days subjects then received placebo tablet for 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 70 kg).
Placebo First, varenicline, + IV Nic	Varenicline	Subjects received a Placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg).After a minimum of a 5 day washout subjects then received varenicline tablet (1mg). once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,0.7 mg per 70kg).
Placebo First, varenicline, + IV Nic	IV Nic	Subjects received a Placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg).After a minimum of a 5 day washout subjects then received varenicline tablet (1mg). once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,0.7 mg per 70kg).
Varenicline first, placebo, + IV Nic	IV Nic	Subjects received Varenicline tablet (1 mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg). After a washout of a minimum of 5 days subjects then received placebo tablet for 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 70 kg).
Placebo First, varenicline, + IV Nic	Placebo	Subjects received a Placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg).After a minimum of a 5 day washout subjects then received varenicline tablet (1mg). once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,0.7 mg per 70kg).
Varenicline first, placebo, + IV Nic	Varenicline	Subjects received Varenicline tablet (1 mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg). After a washout of a minimum of 5 days subjects then received placebo tablet for 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 70 kg).

Primary Outcome Measures

Name	Time	Method
Subjective Responses to Intravenous Nicotine	30 minutes after each nicotine infusion	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.

Secondary Outcome Measures

Name	Time	Method
Mean Reaction Time (RT) on Modified Stroop Task.	pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine)	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).
Heart Rate	30 minutes after each nicotine infusion	The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated.
Changes in Systolic and Diastolic Blood Pressure	30 minutes after each nicotine infusion	The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion.
Cotinine Levels	Before each laboratory session on day 5	Subject Cotinine Levels before each laboratory session.