Nicotine Withdrawal Symptoms and Smoking Relapse
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional

Summary: 
      Background:

      - Smoking is thought to cause changes in the brain that lead to addiction and craving.
      Smokers who try to quit experience nicotine withdrawal symptoms that include irritability,
      anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop
      smoking. Many people say that they continue smoking to help relieve these symptoms, often
      within the first week after trying to quit. Researchers want to study what is happening in
      the brain to cause these symptoms, which may help identify new ways to successfully quit
      smoking.

      Objectives:

      - To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36
      hours.

      Eligibility:

      - Individuals between 18 and 65 years of age who smoke at least 10 cigarettes per day.
      Participants must be able to stop smoking for 36 hours on two occasions.

      Design:

      Phase 1

        -  This study will involve three visits to the National Institute on Drug Abuse.

        -  NOT be able to smoke for 36 hours before the two imaging visits.

        -  Wear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking
           abstinence period and study visits.

        -  Have your blood drawn to test for levels of stress-related hormones.

        -  Complete multiple MRI scanning sessions that last about 1.5 to 2 hours each.

        -  Undergo EEG (brain waves) recording.

        -  Answer questionnaires about how you think and feel.

        -  Complete various tasks and procedures inside and outside of the MRI scanner.

      Phase 2

        -  This study will involve thirteen visits to the National Institute on Drug Abuse.

        -  Set a quit date and develop a treatment plan with a study therapist.

        -  Take Chantix (varenicline) every day for a period of 12 weeks.

        -  Meet for weekly and biweekly counseling sessions with a therapist.

        -  Answer questionnaires about how you think and feel.

      Phase 3

        -  This study will involve three visits to the National Institute on Drug Abuse.

        -  Complete an MRI scanning session that will last about 20min each visit

        -  Meet with a study staff member on each visit who will ask you questions about your
           smoking behavior and how you think and feel.
    

Detailed description: 
      Objective

      The primary objective of the current protocol is to gain a greater understanding of the
      neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the
      maintenance of, or return to smoking behavior among nicotine-dependent individuals, in the
      service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome
      is a major cause of failed quit attempts in smokers, and targeting this time period for
      intervention may help improve smoking cessation outcomes.

      Study Population

      We will recruit treatment seeking and non-treatment seeking smokers, as well as matched
      non-smoker control participants.

      Design

      There are 3 arms included in this protocol, each of which aims to understand the neurobiology
      of the Nicotine Withdrawal Syndrome during the initial quit period, with the broader goal of
      increasing quit success rate in the future.

      Main Study: To understand (1) the acute neurobiological effects of nicotine withdrawal on
      treatment-seeking and non-treatment seeking smokers, (2) the long term neurobiological
      outcomes of varenicline treatment and smoking cessation counseling at 1, 6, and 12 months. We
      will recruit 85 treatment seeking and 35 non-treatment seeking smokers for a within (nicotine
      deprivation), between (treatment-seeking status) subjects randomized, double blind, placebo
      controlled study.

      Motivational Interviewing Arm: (1) To increase motivation and preparation for smoking
      cessation treatment among individuals who express an interest in quitting smoking but are not
      currently ready to enter treatment, in the service of increasing quit success rate and (2) to
      understand the neurobiological basis of motivation to quit smoking, and the interaction
      between motivation to quit and mechanisms that underlie acute nicotine withdrawal. We will
      recruit 300 current smokers interested in quitting smoking, but not yet ready to set a quit
      date.

      Transcranial Direct Current Stimulation (tDCS) Arm: To understand the acute effect of tDCS on
      3 large-scale brain networks dysregulated in nicotine addiction and withdrawal, the Default
      Mode Network, the Executive Control Network, and the Salience Network. We will enroll 60
      non-treatment seeking smokers, with the expectation of 35 completers; and enroll 55
      non-smoking controls, with the expectation of 45 completers, for a double blind, sham
      controlled, randomized crossover study. Smokers will be studied in nicotine abstinence and
      nicotine sated conditions, as in the Main Study design.

      Outcome measures

      Primary outcome measures:

        1. Change in BOLD signal and FC related to task parameters, between drug (or tDCS)
           condition.

        2. Behavioral performance on each of the tasks assessing inhibitory control processes,
           reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making,
           cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward
           bias).

        3. Self-reported craving, withdrawal symptoms and mood/affect

        4. Smoking abstinence as determined by self-reported tobacco use, urine cotinine, and
           breath CO.

      Secondary outcome measures:

        1. MRS for glutamate concentration.

        2. Plasma ACTH and cortisol.

        3. Resting state CBF from ASL.

        4. ERP and EEG measures.

        5. Ratings and scores on self-report characterization measures.

        6. Structural MRI and DTI data.

        7. Resting state FC at 1, 6 and 12 months post-treatment.
    

Intervention name(s): Transcranial Direct Current Stimulation; sham
Intervention type(s): Device; Device
Intervention description(s): Transcranial Direct Current Stimulation (tDCS), a type of Non-invasive Brain Stimulation (NIBS), has the potential to modify neuronal circuits by application of a subthreshold conductive current through the scalp. Two potential targets for tDCS as a smoking cessation aid are the dorsolateral pre-frontal cortex (dlPFC), a node of the ECN, and the ventromedial prefrontal cortex (vmPFC), a node of the DMN. tDCS can potentially strengthen the control of the ECN through excitatory stimulation of the dlPFC, and weaken the influence of the DMN (Lerman et al 2014) by inhibitory stimulation of the vmPFC. The tDCS model we will use is the neuroConn DC-Stimulator MR (neuroCare Group GmbH, Munchen, Germany).; Sham Comparator
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: fMRI; tDCS