Cognitive Remediation With D-Cycloserine
Condition: Smoking Cessation
Intervention: D-cycloserine; Placebo
Intervention description: 2 single weekly doses, 50 mg capsule
Intervention MeSH terms: Cycloserine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: D-cycloserine; Smoking cues; Cognitive remediation; physiologic reactivity; craving

Summary:

      One hundred seventy-five eligible participants will be enrolled with aim of randomizing 60 to
      a double-blind, placebo-controlled trial of D-cycloserine added to cue-exposure treatment to
      prevent relapse to smoking. Subjects who sign an informed consent, meet inclusion criteria,
      and demonstrate response to cue reactivity at the screening visit, will either be:

        -  started on approximately 3 weeks of either nicotine replacement therapy (NRT) at a dose
           of either 14 or 21 mg/day or varenicline titrated to 1.0 mg bid; decision of which
           method to use to quit smoking will be based on participant choice as well as taking into
           account any medical contraindications to either therapy.

        -  evaluated to confirm abstinence from smoking. Recently abstinent participants referred
           by a smoking cessation clinic, PCP or self referred must have an expired air CO < 10 ppm
           to confirm abstinence.

      Subjects who are able to demonstrate 18-24 hours of abstinence prior to the first Cue
      Exposure Therapy Visit (CET I) will be eligible to be randomized to two visits of study
      medication and cue exposure treatment, spaced five to nine days apart. Subjects will complete
      2 follow-up visits at 2-4 days and four weeks after the last CET visit. The entire study
      involves twelve visits and will last approximately ten weeks. For recently abstinent
      participants referred by a smoking cessation clinic, PCP or self referred, the study involves
      7 visits (screening and baseline visit will be merged into one and there is no CBT component)
      and will last approximately 7 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have smoked an average of ≥ 10 cigarettes/day during the past 6
             months

          -  have expired air CO ≥ 10 ppm or urine cotinine ≥ 100 ng/mL

          -  meet DSM-IV criteria for nicotine dependence

          -  aged 18 - 65

          -  Recently abstinent participants referred by a PCP, smoking cessation clinic or self
             referred must have an expired air CO < 10 ppm to confirm abstinence

        Exclusion Criteria:

          -  Severe or uncontrolled medical or psychiatric illness

          -  History of multiple hospitalizations within the last six months for an ongoing medical
             condition

          -  Any significant, current and unstable cardiovascular disease, end stage renal failure,
             severe COPD requiring oxygen, any current unstable neurological disease, a history of
             seizures or epilepsy, or a history of head trauma with lasting neurological sequelae,
             will be excluded for their safety.

          -  Major depressive episode, mania or mixed episode in the prior 6 months

          -  Lifetime history of psychosis, delusional disorder, organic mental disorder by DSM-IV
             criteria, or ongoing cognitive impairment will also be excluded for their safety,

          -  Current excessive use of alcohol (>21 drinks/week in female subjects; >28 drinks/week
             in male subjects)

          -  Current use of illicit drugs.

          -  Current steroid use, current, daily use of benzodiazepines, or participants who are
             unwilling to modify their benzodiazepine use will.

          -  Pregnant or breastfeeding women will be excluded, as well as women of childbearing
             potential who will not use a medically acceptable method of contraception (i.e. IUD,
             oral contraceptives).

          -  Participants who are deaf, blind, or experience any other significant sensory
             impairment that would preclude them from completing study procedures will also be
             excluded, as well as participants who are unable to understand study procedures or
             provide informed consent.

          -  Participants receiving isoniazid or ethionamide, or who have a known sensitivity to
             D-cycloserine.