Pilot Study of Transcranial Magnetic Stimulation (TMS) in Nicotine Addiction
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Treatment for nicotine addiction is characterized by high rates of relapse. New
           treatment therapies for nicotine addiction are exploring the use of brain scanning
           equipment to control and decrease nicotine and cigarette cravings.

        -  Transcranial magnetic stimulation (TMS) uses magnetic pulses to stimulate the brain.
           These pulses can change activity in parts of the brain. Researchers are interested in
           determining whether TMS delivered in single pulses can decrease activity in the parts of
           the brain that respond to nicotine craving.

      Objectives:

      - To determine whether single pulse TMS can reduce cue-induced nicotine craving and use in
      cigarette smokers.

      Eligibility:

        -  Individuals 18 years of age and older who are physically healthy and have smoked 10 or
           more cigarettes per day for at least 1 year.

        -  A small group of healthy nonsmoking control subjects 18 years of age and older will also
           participate in the study.

      Design:

        -  The study will involve seven study visits and two follow-up visits. The control
           participants will have only two visits: one with a magnetic resonance imaging (MRI) scan
           and one with TMS to evaluate brain function and response.

        -  Participants will have an initial assessment about tobacco use habits and craving
           patterns, and will provide blood and urine samples before beginning the study.

        -  Participants will have two initial MRI brain scans. The first scan will look at the
           structure of the brain at rest. During the other scan, participants will look at images
           related to and not related to cigarette smoking.

        -  The single pulse TMS sessions (with either actual TMS or inactive [sham] TMS) will be
           held daily for 5 consecutive days. Magnetic pulses will be triggered by
           cigarette-related picture cues and delivered at varying intervals before the participant
           sees a cigarette-related picture. During these testing visits, researchers will ask
           questions related to tobacco use and craving, and collect urine and breath samples for
           further study.

        -  Participants will have two follow-up visits, 1 week and 2 weeks after the TMS sessions,
           to evaluate memory and mood, and will have one final MRI brain scan at the end of the
           study.
    

Detailed description: 
      Primary objective: Transcranial magnetic stimulation (TMS) provides a non-invasive means of
      inhibiting brain neural activity. This pilot study will test whether 5 days of single pulse
      (sp) TMS reduces cue-induced nicotine craving and use in cigarette smokers.

      Hypothesis: We predict that active spTMS will significantly lower craving for nicotine
      compared with sham spTMS.

      Study population: Subjects will be up to 73 adult cigarette smokers (averaging greater than
      or equal to 10 cigarettes daily for greater than or equal to one year) with current nicotine
      dependence (based on DSM-IV criteria or Faerstrom Test for Nicotine Dependence score greater
      than or equal to 3). Subjects will not have other current major psychiatric disorders or
      substance abuse. Subjects in the pilot phase (one fMRI and one TMS session to valid brain
      mapping procedures) will be up to 25 healthy non-smokers.

      Design: Following a baseline day to evaluate subject characteristics, subjects will be
      randomly assigned to receive 5 days of active or sham spTMS session. spTMS at strength 120
      percent of the motor threshold will be applied to the prefrontal cortex (PFC) using a
      figure-eight coil. Magnetic pulses will be triggered by cigarette-related pictorial cues and
      delivered at varying intervals prior to presentation of a cigarette-related picture. TMS
      pulses will not be delivered during emotionally salient images unrelated to nicotine or
      emotionally neutral images. Brain site localization will use a computerized navigation system
      based on functional and structural MRI scans obtained before the first session. Each session
      (lasting around 20 minutes) will consist of 108 trials (cue presentations): 72 with
      nicotine-associated cues and 18 each with non-drug-associated positive or neutral cues.
      Subjects return for follow-up fMRI and behavioral assessments one and two weeks after the
      final TMS session.

      Outcome measures: The primary outcome measure will be nicotine craving assessed with the
      Tobacco Craving Questionnaire and visual analog scales before and after every TMS session and
      at one- and two-week follow-up. Secondary outcome measures will include cigarette smoking
      over the test period and at follow-up assessed by self-report, salivary cotinine levels, and
      expired breath CO levels. A follow-up fMRI will evaluate changes in regional brain activity
      associated with changes in craving and TMS treatments.

      Benefits: Participants will not directly benefit from this study. This study may contribute
      to better scientific understanding of nicotine addiction and development of better treatment
      methods.

      Risks: The primary risks from TMS are transient headache, scalp discomfort, and hearing loss
      (minimized by wearing ear plugs). Seizures are very rare when spTMS is administered within
      accepted safety guidelines and individuals at increased risk of seizures are excluded. By
      excluding individuals with a history of non-drug-induced mania/ hypomania we minimize the
      risk of inducing a manic episode.
    

Intervention name(s): Transcranial Magnetic Stimulation
Intervention type(s): Device
Intervention description(s): daily sessions for 5 days
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Nicotine; Cigarettes; Tobacco; Transcranial Magnetic Stimulation (TMS); Cue-Induced Craving; Smoking