Varenicline on Reward Responses and Cognition in Adolescent Smokers (GRAND)

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

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorders
• Intervention / Treatment: Drug: Varenicline; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Substance Abuse Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 mg bid placebo titrated over a 2 week period
Active Comparator: varenicline	Drug: Varenicline; 1 mg bid varenicline titrated over a 2 week period; Other Names: Chantix

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

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 18, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (Estimate): June 20, 2012

Study Record Updates

• Last Update Posted (Estimate): February 3, 2014
• Last Update Submitted That Met QC Criteria: January 30, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Adolescent; Magnetic Resonance Imaging; Tobacco; Nicotine; Varenicline
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 1108008929