NCT01202955

Pilot Study of Tolcapone in Smokers

Pilot Study of Tolcapone Effects on Abstinence-Induced Cognitive Symptoms in Smokers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: University of Pennsylvania · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Nicotine Dependence

Interventions

Type	Name	Description
DRUG	Tolcapone	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
DRUG	Placebo	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

Timeline

• Start date: 2008-07-01
• Primary completion: 2009-05-01
• Completion: 2009-06-01
• First posted: 2010-09-16
• Last updated: 2018-09-12
• Results posted: 2011-04-22

Locations

1 site across 1 country: United States