title: Initial Evaluation of Fenofibrate for Efficacy in Aiding Smoking Abstinence.
abstract: BACKGROUND
  Primate and rodent models show that peroxisome proliferator-activated receptor-alpha (PPAR-α) ligands, including fibrate medications, reduce nicotine reinforcement, reward, and related effects. We tested fenofibrate, the most common U.S. Food and Drug Administration-approved fibrate for lipid control versus placebo for initial evidence of efficacy in smoking cessation using a validated cross-over procedure for early Phase 2 evaluations.
  
  
  METHODS
  Adult dependent smokers (N = 38) in this 4-week within-subjects study were those already intending to try to quit in the next 2 months. All smoked ad libitum during weeks 1 (baseline) and 3 (washout) and began fenofibrate (160 mg/d; dosing approved for lipid control) or placebo near the end of weeks 1 and 3. Following each 4-day dose run-up, they were then instructed to try to quit for 4 days (Tuesday-Friday) during weeks 2 and 4, with the order of medication conditions counter-balanced and administered double-blind. Abstinence was verified daily in each 4-day quit period by self-report of no smoking in the prior 24 hours and carbon monoxide < 5 ppm. Secondary measures of acute smoking reinforcement and cue reactivity prior to quitting, and smoking reduction when trying to quit, were also assessed.
  
  
  RESULTS
  No differences between fenofibrate versus placebo were found on days quit (means ± SEM of 1.8±0.3 vs. 1.9±0.3, respectively). Similarly, there were no differences in any of the secondary measures (all P > .20).
  
  
  CONCLUSIONS
  Although higher dosing or other proliferator-activated receptor-alpha agonists may show efficacy, this study indicates that fenofibrate does not aid ability to stop smoking during a brief practice quit period in dependent smokers high in current quit interest.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA; perkinska@upmc.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Karelitz
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Michael
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: Margaret
authors.initials: M
authors.lastname: Fromuth
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Conklin
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: K N Roy
authors.initials: KN
authors.lastname: Chengappa
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh PA;
authors.forename: Chris
authors.initials: C
authors.lastname: Hope
authors.affiliation: Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, Philadelphia PA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000328:Adult; D002248:Carbon Monoxide / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D047493:PPAR alpha / Q000819:agonists*; D057566:Self Report; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000517:prevention & control; D014481:United States; D055815:Young Adult
chemical_list: D047493:PPAR alpha; D002248:Carbon Monoxide; D011345:Fenofibrate