Effects of Varenicline on Smoking Reminders
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Varenicline; Placebo
Intervention description: Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.; Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.
Intervention MeSH terms: Varenicline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Smokers; fMRI; varenicline

Summary:

      Varenicline is the best smoking cessation agent to date; however it is only effective in a
      subgroup of smokers and is associated with undesirable side effects in other subgroups. To
      understand the underlying pharmaco-heterogeneity, the proposed project will use perfusion
      functional magnetic resonance imaging and a functional candidate gene association approach
      using brain, behavioral, and clinical endpoints in a placebo-controlled study of chronic
      varenicline administration in smokers. Brain and behavioral responses to smoking cues will be
      will be significantly greater in 9/10-repeats compared to 10/10-repeats. DAT 9/10-repeat
      smokers receiving varenicline will have better treatment outcome compared to 10/10-repeats.
      For the purposes of the clinical trial portion of the study, the change from cigarettes per
      day at Baseline to the last day of treatment will be reported.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Physically healthy male or female nicotine dependent patients ages 18-60 without other
             current drug dependence or psychiatric diagnosis.

          -  Smoke ≥ 10 cigarettes per day for at least 6 months prior to study start date.

          -  Females must be non-pregnant, non-lactating and either be of non-childbearing
             potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1
             year post-menopausal) or of child bearing potential but practicing a medically
             acceptable method of birth control from at least 2 weeks prior to screening until 30
             days after the last dose of varenicline. Examples of medically acceptable methods for
             this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine
             (IUD), oral contraceptives, levonorgestrel implant, or complete abstinence.

          -  Subjects provide voluntary informed consent.

          -  Subjects must read at 8th grade level or higher.

        Exclusion Criteria:

          -  History of head trauma or injury causing loss of consciousness, lasting more than
             three (3) minutes or associated with skull fracture or inter-cranial bleeding or
             abnormal MRI.

          -  Presence of magnetically active prosthetics, plates, pins, permanent retainer,
             bullets, etc. in patient's body (unless a radiologist confirms that it's presence is
             unproblematic). An x-ray may be obtained to determine eligibility given the
             possibility of a foreign body.

          -  Self report of HIV positive and on medication for symptoms: Determined on an
             individual basis by results from the physical examination and final approval by the
             study physician.

          -  Symptomatic presence of other hematological disease.

          -  Clinically significant hepatic (liver), renal (kidney), neurological, or
             endocrinological abnormalities.

          -  History of any cardiovascular event within the last 6 months and any
             serious/significant cardiovascular event in the subject's life. This will be
             determined on an individual basis by the study physician.

          -  History of psychosis or seizures.

          -  Use of medications or natural herbs that may cause sedation or may effect the brain
             systems that are being studied (medication use will be evaluated on a case-by-case
             basis).

          -  Claustrophobia or other medical condition preventing subject from lying in the MRI for
             approximately one (1) hour.