Neural Substrates in Nicotine Withdrawal
Condition: Tobacco Use Disorder
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test the hypothesis that a medication called tolcapone (Brand Name: Tasmar)
      will help reduce cognitive problems that smokers experience when they quit. This study will
      also determine whether the benefits of this medication differ depending on a smokers' genetic
      background.
    

Detailed description: 
      Tolcapone, an FDA-approved treatment for Parkinson's disease, improves cognitive performance
      in healthy controls with COMT val/val genotypes, putatively by increasing prefrontal dopamine
      levels. We propose a within-subject double-blind cross-over neuroimaging study of short-term
      (11 days) treatment with tolcapone (vs. placebo).

      Thirty chronic smokers (15 with val/val genotypes and 15 with val/met or met/met genotypes)
      will undergo blood oxygenation level dependent (BOLD) fMRI during the two medication periods:

        1. after 24 hours of monitored abstinence while on tolcapone, and

        2. after 24 hours of monitored abstinence while on placebo (medication order
           counterbalanced with at least a 10-day washout).

      The BOLD fMRI data will be acquired while subjects perform a working memory task (Fractal
      N-back), a sustained attention task (Continuous Performance Task; CPT), and a response
      inhibition task (Go/No-Go). The primary outcome is medication effects (within subject) on
      task-related BOLD activation after 24 hours of abstinence. Changes in behavioral performance
      and subjective symptoms will be examined in relation to brain activity changes.

      The proposed study will provide a critical mechanistic understanding of the role of COMT in
      abstinence-induced cognitive symptoms that promote smoking relapse. Information obtained in
      this study may further establish cognitive performance measures as endophenotypes for
      nicotine dependence.
    

Intervention name(s): Tolcapone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants will be asked to take study medication each day for both 11-day study medication periods.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take tolcapone during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by tolcapone during the second medication period.; Participants will be asked to take study medication each day for both 11-day study medication periods.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take tolcapone during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by tolcapone during the second medication period.
Other intervention name(s): Tasmar
Intervention MeSH terms: Tolcapone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Genetics; Nicotine; Cognition; fMRI