Varenicline on Reward Responses and Cognition in Adolescent Smokers

Study Overview
=================
Brief Summary
-----------------
This is a pilot project using functional magnetic resonance imaging (fMRI) to examine the influence of varenicline on reward processing, cognitive control, and regulation of craving in adolescent smokers. We hypothesize that adolescent smokers receiving varenicline, when compared with those receiving placebo, will have differential brain responses to anticipation of rewards, during exposure to the Stroop task, and in response to tobacco cues.

Detailed Description
-----------------
This is a pilot project using functional magnetic resonance imaging (fMRI) to examine the influence of varenicline on reward processing, cognitive control, and regulation of craving in adolescent smokers. We hypothesize that adolescent smokers receiving varenicline, when compared with those receiving placebo, will have increased activation of the ventral striatum (VS) in response to anticipation of rewards in the Monetary Incentive Delay Task (MIDT), decreased activation of the dorsolateral prefrontal cortex (dlPFC) during exposure to incongruent stimuli in the Stroop task, and reduced activation of the ventral striatum in response to tobacco cues, and increased activation of the dlPFC during regulation of responses to tobacco cues during the Regulation of Craving (ROC) task. The results of this pilot project will have important implications regarding the use of varenicline for treating tobacco dependence and understanding varenicline's neurobiological effects in adolescent smokers.

Official Title
-----------------
Examining the Effects of Varenicline on Reward Responses,Cognition, and Tobacco Cues in Adolescent Smokers

Conditions
-----------------
Tobacco Use Disorders

Intervention / Treatment
-----------------
* Drug: Varenicline
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between 16-19 years of age Able to read and write English Smoking 5 or more cigarettes on a daily basis, for at least one year Not seeking smoking cessation treatment Weighing > 55 kg (121 lbs) Exclusion Criteria: Current criteria for abuse or dependence on another psychoactive substance. Current diagnosis of any clinical significant psychiatric disease like major depressive disorder, panic or anxiety disorder, psychosis, schizophrenia, bipolar disorder. Those with a prior suicide attempt or with active suicidal ideation at baseline Any regular use of any psychoactive drugs including anxiolytics and antidepressants Pregnant or lactating girls: females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least 14 days prior to study medication administration until 30 days after the last dose of study medication. Acceptable methods of contraception are: abstinence; any form of hormonal contraception such as Depo-Provera, daily oral contraceptive, transdermal patch, or Nuva-ring; intra-uterine device, sterilization; or double barrier contraception which is a combination of any two of the following methods: condoms, spermicide, diaphragm. Evidence or history of clinically significant neurological, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, or allergic disease. History of prior use of or sensitivity to varenicline. Color-blindness History of significant head trauma Metal in body Other medical conditions contra-indicated for MRI Past history of marked irritability or agitation when attempting to quit smoking, determined by the Minnesota Nicotine Withdrawal Questionnaire.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: varenicline<br> | Drug: Varenicline<br>* 1 mg bid varenicline titrated over a 2 week period<br>* Other names: Chantix;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 mg bid placebo titrated over a 2 week period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neural responses to the MIDT | The Monetary Incentive Delay Task (MIDT) will be administered during the fMRI at the end of 14 days of varenicline treatment | During MRI following14 days of varenicline treatment | 
| neural responses to the ROC | The Regulation of Craving (ROC)will be administered during the fMRI at the end of 14 days of varenicline treatment | During MRI following14 days of varenicline treatment | 
| neural responses to the Stroop | The Stroop will be administered during the fMRI at the end of 14 days of varenicline treatment | During MRI following14 days of varenicline treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tobacco, Adolescent, Nicotine, Magnetic Resonance Imaging, Varenicline