Pilot Study of Tolcapone in Smokers
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      The goals of this within-subject pilot study are: (1) assess the feasibility and safety of
      administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and
      (2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms
      that promote relapse. A secondary exploratory goal is to assess whether these effects may be
      more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT
      val/val.
    

Detailed description: 
      Despite decades of research to develop pharmacotherapies for nicotine dependence (ND), with
      current FDA approved medications (bupropion, varenicline and NRTs) the majority (>60%) of
      smokers relapse in the first year following treatment (Lerman, Patterson et al. 2005;
      Tonstad, Tonnesen et al. 2006). Testing novel medications that may reduce abstinence symptoms
      that prompt smoking relapse is a plausible route to identifying new treatments for nicotine
      dependence. The goals of this within-subject pilot study are: (1) assess the feasibility and
      safety of administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to
      smokers, and (2) explore whether tolcapone may reduce abstinence-induced cognitive and
      affective symptoms that promote relapse. A secondary exploratory goal is to assess whether
      these effects may be more pronounced in smokers who carry a high risk COMT genotype for
      smoking relapse: COMT val/val. Sixteen smokers (8 met/met genotype and 8 val/val genotype)
      who meet study eligibility criteria will complete two 10-day medication periods: one while
      taking tolcapone and one while taking placebo (order counterbalanced). The testing session
      will occur on day 7 of each medication phase and include three computerized tasks.
      Participants will be asked to refrain from smoking for at least 14 hours (overnight) prior to
      the testing day in each medication phase. There will be a 3-day medication taper on days 8-10
      of each medication period, followed by a washout period of at least 7 days between medication
      periods. The main outcomes to be evaluated are participant enrollment and retention, side
      effects, and performance on computerized tasks. Positive results from this pilot study would
      provide a basis for a larger scale investigation to assess the efficacy of tolcapone as a
      medication that ameliorates abstinence induced neurocognitive symptoms in smokers.
    

Intervention name(s): Tolcapone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day; Day 1 100mg three times per day Day 2 - Day 7 200mg three times per day Day 8 200mg twice a day Day 9 200mg once a day Day 10 100mg once a day
Other intervention name(s): Tasmar
Intervention MeSH terms: Tolcapone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Smoking, Abstinence