Initial Screening of Gemfibrozil as a Novel Treatment for Tobacco Addiction
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to investigate the effect of gemfibrozil on nicotine
      reinforcement and cue-elicited craving. Other objectives of this study include screening for
      the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt and
      examining the validity of using laboratory measures of tobacco dependence to predict smoking
      abstinence. It is hypothesized that gemfibrozil will result in diminished nicotine
      reinforcement, an attenuated response to smoking cues, and an increase in smoking abstinence
      compared with placebo. It is also hypothesized that the laboratory measures will prove valid
      in predicting abstinence.
    

Detailed description: 
      Animal studies have shown that drugs acting as agonists at alpha-type peroxisome
      proliferator-activated receptors (PPARα) suppress nicotine self-administration, attenuate
      relapse to nicotine-seeking behavior in the reinstatement model, and block nicotine-induced
      neuronal firing and dopamine release in reward pathways of the brain. These results have been
      demonstrated with synthetic PPARα agonists and with fibrate drugs (clofibrate, fenofibrate),
      which are used clinically to treat elevated cholesterol and triglycerides levels. Thus, PPARα
      is a potential target for the treatment of tobacco addiction. This is the first human study
      to investigate whether a fibrate drug (gemfibrozil, Lopid®) can reduce nicotine reward and
      aid smokers in becoming tobacco abstinent.

      The objectives of this study are:

        1. to investigate the effect of gemfibrozil on laboratory measures of nicotine
           reinforcement and cue-elicited craving

        2. to screen for the ability of gemfibrozil to aid smoking abstinence during a brief quit
           attempt

        3. to examine the validity of using laboratory measures of tobacco dependence to predict
           smoking abstinence and possible gemfibrozil-related increases in smoking abstinence

      This outpatient study will be conducted at the Center for Addiction and Mental Health (CAMH)
      in Toronto, Canada. This site will enroll 40 adult smokers who intend to quit smoking in the
      next 3 months.

      The study is a double-blind, placebo-controlled, crossover design comparing the effects of
      gemfibrozil and placebo. The study will comprise two 2-week medication phases with a washout
      period of at least one week. At the end of the first medication week laboratory measures will
      be taken and during the second medication week participants will make a quit attempt and
      abstinence will be assessed.

      Outcome measures include laboratory assessments of nicotine reinforcement and smoking cue
      reactivity. The measure of nicotine reinforcement is the percentage of nicotine cigarette
      puffs chosen during a forced-choice task. Measures of cue reactivity include tobacco craving,
      mood, and autonomic responsivity. Other measures are days of smoking abstinence during the
      quit-attempt weeks. Abstinence is assessed by self-reports of no smoking and by breath carbon
      monoxide < 5 ppm on clinic visits. Other assessments of abstinence include self-reported
      tobacco craving and withdrawal.
    

Intervention name(s): Gemfibrozil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 600 mg of gemfibrozil (one capsule) twice daily for two weeks.; One lactose pill twice a day for two weeks.
Other intervention name(s): Lopid; Lactose
Intervention MeSH terms: Gemfibrozil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Gemfibrozil; Nicotine Dependence; Smoking; Cigarettes