Varenicline and Nicotine Interactions in Humans (VA)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Varenicline Attenuates Some of the Subjective and Physiological Effects of Intravenous Nicotine in Humans.

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Varenicline
* Drug: Placebo
* Drug: IV Nic


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo First, varenicline, + IV Nic<br>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). | Drug: Varenicline<br>* Varenicline (1 mg per day) given for 4 days prior to laboratory session<br>* Other names: Chantix;Drug: Placebo<br>* Sugar Pill<br>* Other names: Sugar Pill;Drug: IV Nic<br>* IV Nicotine given during the laboratory session following 4 days of exposure to the study medication (varenicline or placebo). This nicotine was given during each laboratory session which followed the 4 days of exposure to either placebo then varenicline or varenicline then placebo.<br>* Other names: IV Nicotine;|
| Experimental: Varenicline first, placebo, + IV Nic<br>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). | Drug: Varenicline<br>* Varenicline (1 mg per day) given for 4 days prior to laboratory session<br>* Other names: Chantix;Drug: Placebo<br>* Sugar Pill<br>* Other names: Sugar Pill;Drug: IV Nic<br>* IV Nicotine given during the laboratory session following 4 days of exposure to the study medication (varenicline or placebo). This nicotine was given during each laboratory session which followed the 4 days of exposure to either placebo then varenicline or varenicline then placebo.<br>* Other names: IV Nicotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Responses to Intravenous Nicotine | 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. | 30 minutes after each nicotine infusion | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapeutic effects