Pharmacogenetics, Emotional Reactivity and Smoking
Condition: Tobacco Use Disorder; Smoking Cessation
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The goals of this placebo-controlled randomized clinical trial were to evaluate the
      differences in emotional reactivity (peak startle response to affective stimuli) during a
      cessation attempt among smokers treated with bupropion, varenicline, or placebo, and to
      determine if these differences were moderated by genotype.
    

Detailed description: 
      Bupropion and Varenicline are smoking cessation aids that may help people to quit smoking.

      During the orientation visit, the study will be explained to you and you will be given an
      opportunity to ask, and have answered, any questions you may have. You will also be asked to
      give a buccal (cheek cell) sample for genetic analysis. This session will last about 1.5
      hours.

      During the screening visit, you will be asked questions about your health, medication use,
      smoking history, and tobacco use. You will be asked about any current or past feelings of
      depression. Also, a small blood sample will be drawn (about 2 tablespoons) from your upper
      arm for a liver and kidney function test and a saliva sample will be collected to measure
      whether you are smoking. Women who are able to have children must have a negative urine
      pregnancy test. This session will last about 2.5 hours.

      If you are eligible to take part in the study, you will be randomly assigned (as in the toss
      of a coin) to one of three treatment groups. Participants in the first group will receive
      Bupropion. Participants in the second group will receive Varenicline. Participants in the
      third group will receive a placebo. A placebo is a substance that looks like the study drug
      but which has no active ingredients. You will have an equal chance of being assigned to the
      Bupropion, Varenicline, or placebo treatment group. Neither you nor your counselor will know
      to which group you were assigned.

      All participants will take study pills (either Bupropion, Varenicline, or placebo) by mouth
      for 12 weeks. The dose of study medication may or may not change during the study. You will
      be responsible for returning any unused, used, or partly used study medication bottles to a
      study staff member.

      All participants will receive smoking cessation counseling to help them quit smoking, in the
      form of both in-person and telephone counseling sessions. Some of the counseling sessions may
      be videotaped or audio-taped. The videotapes will be used to help the investigators make sure
      that the counselors are following the correct procedures and will be erased within one year
      following your completion of the study. No one but the study investigators or those delegated
      by the study investigators will be allowed to view the tapes and the identity of the
      participants will be kept strictly confidential. Staff that may be given permission to view
      the tapes include project staff, consultants that review and rate how well the study
      counselors follow guidelines, and/or consultants that review how well the assessments are
      given.

      You will need to come to the Behavioral Science Research Clinic at M. D. Anderson for 9
      clinic visits over an 8-month period. You will receive 5 telephone calls from the study staff
      (while in treatment and during follow-up) to check on your progress in quitting smoking.

      You will complete your first lab evaluation session (baseline) before any treatment begins
      (while you are still smoking). Immediately after the baseline lab session (on the same day),
      you will begin to receive counseling to quit smoking. You will begin taking one of the 3
      study medications (Bupropion, Varenicline, or placebo) the next morning.

      There will be 3 lab sessions, during which you will be asked to complete questionnaires about
      your mood and feelings (about 30 minutes total). Also, you will give a breath sample by
      blowing air into a small tube. This sample shows how much you have smoked. In each session
      you will be asked to watch slides and listen to a series of tones through earphones. The
      slides will include pictures of people, nature scenes, and artwork. Slides showing victims of
      car crashes, medical procedures, and nude people will also be shown. You will be shown
      examples of these slides before beginning the procedure and given the opportunity to withdraw
      from the study. During the lab sessions, your heart rate, brain electrical activity (EEG),
      skin sweating, and muscle tension will be monitored. To do this, small sensors will be placed
      on the fingers, arms, scalp and face. You should not drink more than 2 cups of coffee or
      other caffeine drinks at least 2.5 hours before each session.

      During the first counseling visit, you will set a quit date for stopping smoking about 2
      weeks after starting your study medication. You are asked not to quit smoking before the set
      quit date. After your quit date, you are asked to stay smoke free. You are asked to attend
      all your sessions whether you are smoking or not. All participants will receive smoking
      cessation counseling in the form of both in-person and telephone counseling sessions. The
      purpose of these visits will be to prepare you for quitting and to check the effects of the
      study medication on your attempt to stop smoking.

      At each of your clinic visits, your blood pressure will be taken and you will be asked to
      blow air through a carbon monoxide (CO) measuring device. CO is a gas that is found in higher
      levels among cigarette smokers. At several visits you will be asked to provide a saliva
      sample to check for cotinine, a chemical produced by the breakdown of nicotine during
      smoking. You will be asked to give a saliva sample in a collection tube. Like the CO test,
      this test will help researchers measure how much you are smoking.

      At your visits you will be asked questions about your smoking behavior. You will also be
      asked questions about your health and medical condition, and about any medications you are
      taking. You will be asked to complete a daily diary on cigarette smoking and drug dosing.

      You will also be asked to mail saliva samples back to the clinic at least two times after
      stopping the medication. This will allow researchers to check on your smoking status.

      Your total participation in this study will last about 8 months. This will include a 3-month
      and 6-month follow-up visit after your scheduled quit date. If the study staff is not able to
      reach you by phone, mail, or the information provided by your contacts, they may try to
      locate you through telephone directory assistance (411) or internet search sources (for
      example, Google or Yahoo!), which use information from the public domain (meaning everyone
      has access to it). If the study staff is still unable to find you, they may use a locator
      service such as Transunion or the National Change of Address (NCOA) database maintained by
      the United States Postal Service, as a last resort. Transunion uses magazine subscriptions
      and credit applications to find new addresses, and the NCOA uses the Change of Address cards
      filed with the post office when a person moves and requests their mail be forwarded to a new
      address. If the study staff has to use either of these services, they would only disclose
      your name and last known address.

      At the end of the study, you will be able to ask additional questions about the results of
      the study and about procedures you have experienced during the study. Additionally, you will
      be able to sign up to receive a copy of the paper that will be written at the completion of
      the study.

      This is an investigational study. Up to 375 smokers will take part in this study. All will be
      enrolled at MD Anderson.
    

Intervention name(s): Bupropion; Varenicline; Placebo; Smoking Cessation Counseling
Intervention type(s): Drug; Drug; Drug; Behavioral
Intervention description(s): Starting dose 150 mg by mouth daily (150 mg every morning for three days; 150 mg twice a day thereafter); Starting dose 0.5 mg by mouth daily (0.5 mg every morning for days 1 - 3, then 0.5 mg twice a day for days 4 - 7, then 1 mg twice a day thereafter); Placebo by mouth for 12 weeks.; Counseling over 8 months and telephone support calls.
Other intervention name(s): Wellbutrin; Wellbutrin SR; Zyban; Chantix
Intervention MeSH terms: Bupropion; Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pharmacogenetics; Emotional Reactivity; Smoking Cessation Counseling; Smoking; Bupropion; Wellbutrin; Wellbutrin SR; Zyban; Varenicline; Chantix; Placebo