Clinical trial NCT00606892: Varenicline and Nicotine Interactions in Humans (VA)
Official title: Varenicline Attenuates Some of the Subjective and Physiological Effects of Intravenous Nicotine in Humans.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking Cessation
Keywords: therapeutic effects
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: US Department of Veterans Affairs
name: National Institute on Drug Abuse (NIDA)
First posted: 2008-02-05
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Subjective Responses to Intravenous Nicotine
timeFrame: 30 minutes after each nicotine infusion
Secondary outcomes:
measure: Mean Reaction Time (RT) on Modified Stroop Task.
timeFrame: pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine)
measure: Cotinine Levels
timeFrame: Before each laboratory session on day 5
measure: Heart Rate
timeFrame: 30 minutes after each nicotine infusion
measure: Changes in Systolic and Diastolic Blood Pressure
timeFrame: 30 minutes after each nicotine infusion
Other outcomes:
Locations:
city: West Haven
country: United States
facility: Veterans Affairs Hospital
state: Connecticut
Study officials:
affiliation: Yale University Associate Professor
name: Mehmet Sofuoglu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sofuoglu M, Herman AI, Mooney M, Waters AJ. Varenicline attenuates some of the subjective and physiological effects of intravenous nicotine in humans. Psychopharmacology (Berl). 2009 Nov;207(1):153-62. doi: 10.1007/s00213-009-1643-z. Epub 2009 Aug 20.